PD 0332991 and Anastrozole for Stage 2 or 3 Estrogen Rece... | NCT01723774

Name	Class
Pfizer	INDUSTRY

Label	Type	Description	Intervention Names
Arm 1: PIK3CA Wild Type Cohort	Experimental	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.	Drug: PD0332991 Drug: Anastrozole Drug: Goserelin Procedure: Surgery (standard of care) Procedure: Tumor biopsy
Arm 2: PIK3CA Mutant Type Cohort	Experimental	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Name	Type	Description	Arm Group Labels	Other Names
PD0332991	Drug		Arm 1: PIK3CA Wild Type Cohort Arm 2: PIK3CA Mutant Type Cohort Arm 3: Endocrine Resistant Cohort

Measure	Description	Time Frame
Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (PIK3CA Wild Type Cohort Only)	Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991	At cycle 1 day 15 (2 weeks)
Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (Endocrine Resistant Cohort Only)	Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991	At cycle 1 day 15 (2 weeks)

Measure	Description	Time Frame
Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 ( PIK3CA Mutant Type Cohort Only)	Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991	At cycle 1 day 15 (2 weeks)
Number of Participants With Complete Cell Cycle Arrest

Eligibility Module

Eligibility Criteria

Pre-registration PIK3CA Mutant Inclusion

Clinical T2-T4c, any N, M0 invasive ER+ (Allred Score of 6-8) and HER2 negative (0 or 1+ by IHC or FISH negative for amplification) breast cancer, by AJCC 7th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node. Note: Patients with invasive ER+ (Allred Score of 6-8) HER2- breast cancer or DCIS in the contralateral breast the patient are eligible
Female ≥18 years of age
ECOG performance status of 0, 1 or 2
Life expectancy > 4 months
Premenopausal, patient must be willing to comply with pregnancy requirements
Adequate organ and marrow function
- leukocytes ≥ 3,000/mcL
- absolute neutrophil count ≥ 1,500/mcL
- platelets ≥ 100,000/mcL
- total bilirubin ≤ ULN
- AST(SGOT)/ and ALT(SGPT) < 2.5 X ULN
- Creatinine ≤ ULN
Able to understand and willing to sign an IRB-approved written informed consent document

Exclusion

Prior treatment of this cancer including: surgery, radiation, chemotherapy, biotherapy, hormonal therapy, investigational agent prior to study entry
Receiving any investigational agents
Prior therapy with any Cdk4 inhibitor
Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism
Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements
Pregnant/nursing
Unwilling to employ adequate contraception
Known HIV-positive on combination antiretroviral therapy
Evidence of inflammatory cancer
Known metastatic disease
Current use of anticoagulation therapy
Previous excisional biopsy of the breast cancer or sentinel lymph node biopsy
Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption)
History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991 or other agents used in the study
Corrected QT interval >470 msec

Registration PIK3CA Mutant Inclusion The criteria below must be met in addition to the pre-registration criteria, except treatment with endocrine therapy for this cancer is allowed prior to registration

PIK3CA mutant cohort: tumor PIK3CA mutation present
Premenopausal women, serum estradiol level in postmenopausal range ≤ 7 days prior to registration

Exclusion Criteria below must be met in addition to the pre-registration criteria -Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort)

PIK3CA Wild Type Inclusion

Clinical T2-T4c, any N, M0 invasive ER+ (Allred Score of 6-8) and HER2 negative (0 or 1+ by IHC or FISH negative for amplification) breast cancer, by AJCC 7th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node. Note: Patients with invasive ER+ (Allred Score of 6-8) HER2- breast cancer or DCIS in the contralateral breast the patient are eligible
For the PIK3CA wild type cohort: tumor PIK3CA mutation absent. Note that if a patient did not have sufficient research tissue for PIK3CA sequencing at pre-registration or if PIK3CA sequencing result is delayed, she could be registered and enrolled on the PD991 trial without assigning to a particular cohort at the time of enrollment. PIK3CA sequencing will be performed in the future on tumors collected at subsequent time points to assign the treatment cohort or when the PIK3CA sequencing data is available
For the endocrine resistant cohort: Ki67 > 10% by central testing at Washington University AMP laboratory from a tumor biopsy performed after at least 2 weeks on neoadjuvant endocrine therapy. Note that prior neoadjuvant endocrine therapy could include any endocrine therapy (including aromatase inhibitor, tamoxifen, fulvestrant) alone or in combination, or endocrine therapy in combination with any investigational agent that is not a Cdk 4/6 inhibitor

*Patients who had a Day 17 Ki67 > 10% from the NCI9170 trial are eligible for the endocrine resistant cohort
Female >18 years of age
ECOG performance status of 0, 1 or 2
Life expectancy > 4 months
If premenopausal, patient must be willing to comply with pregnancy requirements
Adequate organ and marrow function:
- leukocytes ≥ 3,000/mcL
- absolute neutrophil count ≥ 1,500/mcL
- platelets ≥ 100,000/mcL
- total bilirubin ≤ ULN
- AST(SGOT)/ and ALT(SGPT) < 2.5 X ULN
- Creatinine ≤ ULN
In premenopausal women, serum estradiol level in postmenopausal range ≤ 7 days prior to registration.
Able to understand and willing to sign an IRB-approved written informed consent document

Exclusion

Prior treatment of this cancer including: Surgery, Radiation therapy, Chemotherapy, Biotherapy, Hormonal therapy, Investigational agent prior to study entry
Receiving any other investigational agents
Prior therapy with any Cdk4 inhibitor
Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism
Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements
Pregnant/nursing
Unwilling to employ adequate contraception
Known HIV-positive on combination antiretroviral therapy
Evidence of inflammatory cancer
Known metastatic disease
Current use of anticoagulation therapy
Previous excisional biopsy of the breast cancer or sentinel lymph node biopsy
Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption)
History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991 or other agents used in the study
Corrected QT interval >470 msec
Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort)

Endocrine Resistant Inclusion

Clinical T2-T4c at diagnosis or screening, any N, M0 invasive ER+ (Allred Score at least 3 or > 1% ER positivity) and HER2 negative (0 or 1+ by IHC or FISH negative or equivocal) breast cancer, by AJCC 7th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node. Note: Patients with invasive breast cancer that is ER pos, HER2 neg or equivocal or DCIS in the contralateral breast are eligible; multi-focal diseases are not excluded. The dominant lesion will be followed per protocol
Ki67 > 10% by central testing at Washington University AMP laboratory from a tumor biopsy performed after at least 2 weeks on neoadjuvant endocrine therapy. If Ki67 is > 10% by local testing, the Ki67 slide and H&E slide need to be reviewed by the study pathologist to confirm eligibility (discuss with Study Chair). For patients external to Washington University, please contact the Washington University coordinator by email so that a screening ID# can be assigned prior to shipment of the slides
Female ≥ 18 years of age
ECOG performance status of 0, 1 or 2
Pre- or post-menopausal women are eligible. If premenopausal, patient must be willing to comply with pregnancy requirements and agrees with GnRH agonist therapy for ovarian suppression during the study
Adequate organ and marrow function:
- Leukocytes ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ ULN
- AST(SGOT)/ and ALT(SGPT) < 2.5 X ULN
- Creatinine ≤ ULN
Able to understand and willing to sign an IRB-approved written informed consent document

Exclusion

Prior treatment of this cancer including: Surgery, Radiation, Chemotherapy
Receiving any other investigational agents
Prior therapy with Cdk4 inhibitor
Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism
Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements
Pregnant/nursing
Unwilling to employ adequate contraception
Known HIV-positive on combination antiretroviral therapy
Known metastatic disease
Current use of anticoagulation therapy
Previous excisional biopsy of the breast cancer or sentinel lymph node biopsy
Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption)
History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991 or other agents used in the study
Corrected QT interval >470 msec
Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort)

Adjuvant Inclusion

Derived benefit from PD 0332991 in the neoadjuvant setting in this trial. This includes the 26 patients who achieved complete cell cycle arrest only after the addition of PD 0332991 (C1D1 Ki67 >2.7% and C1D15 Ki67 ≤ 2.7%) from the main study (PIK3CA WT, mutant, or unknown cohorts) as well as any patients who have a Ki67 ≤ 10% on C1D15 biopsy in the endocrine resistant cohort
ECOG performance status of 0, 1 or 2
Premenopausal, patient must be willing to comply with pregnancy requirements laid out
Adequate organ and marrow function
- leukocytes ≥ 3,000/mcL
- absolute neutrophil count ≥ 1,500/mcL
- platelets ≥ 100,000/mcL
- total bilirubin ≤ ULN
- AST(SGOT)/ and ALT(SGPT) ≤ 2.5 X ULN
- Creatinine ≤ ULN
Underwent surgery of the breast and axilla for curative intent
At least 4 weeks post completion of adjuvant chemotherapy and radiation therapy if indicated
Patients who already started on adjuvant hormonal therapy are eligible under the following conditions:
- For the 26 patients who enrolled in the initial cohorts and derived benefit from neoadjuvant PD 0332991 (C1D1 Ki67 >2.7% and C1D15 Ki67 ≤ 2.7%), adjuvant PD 0332991 should be initiated as soon as possible if adjuvant hormonal therapy has been initiated and the patient has completed radiation if indicated
- For patients who enrolled in the endocrine resistant cohort and derived benefit from neoadjuvant PD 0332991 (C1D15 Ki67 ≤ 10%), adjuvant PD 0332991 should be initiated within 6 months or sooner after initation of adjuvant hormonal therapy
Able to understand and willing to sign an IRB-approved written informed consent document

Exclusion

Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism
Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, ssychiatric illness/social situations that would limit compliance with study requirements
Pregnant/nursing
Unwilling to employ adequate contraception
Known HIV-positive on combination antiretroviral therapy. -Known metastatic disease
Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption)
History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991 or other agents used in the study
Corrected QT interval >470 msec
Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort)

Name	Affiliation	Role
Cynthia X Ma, M.D., Ph.D.	Washington University School of Medicine	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama		Birmingham	Alabama	35233	United States
Mayo Clinic - Scottsdale

PubMed Identifier	Type	Citation	Retractions
29162134	Derived	Bagegni N, Thomas S, Liu N, Luo J, Hoog J, Northfelt DW, Goetz MP, Forero A, Bergqvist M, Karen J, Neumuller M, Suh EM, Guo Z, Vij K, Sanati S, Ellis M, Ma CX. Serum thymidine kinase 1 activity as a pharmacodynamic marker of cyclin-dependent kinase 4/6 inhibition in patients with early-stage breast cancer receiving neoadjuvant palbociclib. Breast Cancer Res. 2017 Nov 21;19(1):123. doi: 10.1186/s13058-017-0913-7.

Label	URL
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine	View source

ID	Title	Description
FG000	Arm 1: PIK3CA Wild Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jun 29, 2022

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (PIK3CA Wild Type Cohort Only)

Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991

Arm 2 and Arm 3 participants were not evaluable for this outcome measure as it is for Arm 1: PIK3CA Wild Type Cohort only. 5 participants in Arm 1 were not evaluable. 1 participant was not evaluable due to insufficient quality of specimen, 1 participant was not evaluable because she withdrew prior to starting treatment, 2 participants were not evaluable because there was no tumor present on biopsy, and 1 participant was not evaluable because she withdrew prior to cycle 1 day 15 biopsy.

Posted

Count of Participants

Participants

At cycle 1 day 15 (2 weeks)

ID	Title	Description
OG000	Arm 1: PIK3CA Wild Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
OG001	Arm 2: PIK3CA Mutant Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
OG002	Arm 3: Endocrine Resistant Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Units	Counts
Participants	OG00029 OG0010 OG0020

Title

Denominators

Categories

Title	Measurements
	OG00023

Primary

Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (Endocrine Resistant Cohort Only)

Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991

Arm 1 and Arm 2 participants were not evaluable for this outcome measure as it is for Arm 3: Endocrine Resistant Cohort only. 1 participant was not evaluable for this outcome measure as the participant did not have any tissue available at the cycle 1 day 15 biopsy.

Posted

Count of Participants

Participants

At cycle 1 day 15 (2 weeks)

ID	Title	Description
OG000	Arm 1: PIK3CA Wild Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
OG001

Secondary

Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 ( PIK3CA Mutant Type Cohort Only)

Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991

Arm 1 and Arm 3 participants were not evaluable for this outcome measure as it is for Arm 2: PIK3CA Mutant Type Cohort only.

Posted

Count of Participants

Participants

At cycle 1 day 15 (2 weeks)

ID	Title	Description
OG000	Arm 1: PIK3CA Wild Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
OG001	Arm 2: PIK3CA Mutant Type Cohort

Secondary

Number of Participants With Complete Cell Cycle Arrest

Compare rate of complete cell cycle arrest (defined as Ki67 ≤ 2.7%) arrest between C1D1 and C1D15

PIK3CA Wild Type Cohort - 5 participants not evaluable. 1 due to insufficient quality of specimen, 1 because she withdrew prior to starting treatment, 2 participants because there was no tumor present on biopsy, and 1 because she withdrew prior to cycle 1 day 15 biopsy. Endocrine Resistant Cohort-1 participant because no tissue available at the cycle 1 day 15 biopsy.

Posted

Count of Participants

Participants

Cycle 1 day 1 and cycle 1 day 15 (2 weeks)

ID	Title	Description
OG000	Arm 1: PIK3CA Wild Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Secondary

Clinical Response Rate

The clinical response rate is the number of patients whose disease meets the WHO criteria of complete or partial response prior to surgery divided by the total number of eligible patients who began combination neoadjuvant treatment.
Complete Response (CR) is defined as the disappearance of all known disease based on a comparison between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there is no appearance of new lesions.
Partial Response (PR) is defined as a 50% or greater decrease in the product of the bidimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there can be no appearance of new lesions or progression of any lesion.

7 participants in Arm 1 were not evaluable for this outcome measure. 3 participants in Arm 2 were not evaluable for this outcome measure. 12 participants in Arm 3 were not evaluable for this outcome measure. Reasons include patient withdrawal (n=4), progressive disease during cycle 1 (n=2), cycle 1 day 15 Ki67 >10% (n=14) high estradiol (n=1), and adverse event (n=1).

Posted

Count of Participants

Participants

16 weeks

ID	Title	Description
OG000	Arm 1: PIK3CA Wild Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Secondary

Radiologic Response Rate

The radiological response rate is the number of patients whose disease meets with WHO criteria for complete or partial response at the evaluation prior to surgery divided by the total number of eligible patients who began combination neo-adjuvant therapy.
Complete Response (CR) is defined as the disappearance of all known disease based on a comparison between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there is no appearance of new lesions.
Partial Response (PR) is defined as a 50% or greater decrease in the product of the bidimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there can be no appearance of new lesions or progression of any lesion.

Arm 1 PIK3CA Wild Type Cohort: 23 participants not evaluable due to imaging not being performed. Arm 2 PIK3CA Mutant Type Cohort: 9 participants not evaluable due to imaging not being performed. Arm 3 Endocrine Resistant Cohort: 10 participants not evaluable due to imaging not being performed.

Posted

Count of Participants

Participants

At the end of cycle 4 prior to surgery (estimated to be 16 weeks)

ID	Title	Description
OG000	Arm 1: PIK3CA Wild Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Secondary

Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events

The maximum grade for each type of adverse event will be recorded for each patient using the NCI-CTCAE v4.0 coding scheme, and frequency tables will be reviewed to determine patterns. Additionally, the relationship (possibly related, probably related, and definitely related) of the adverse event(s) to the study treatment will be taken into consideration.

Posted

Count of Participants

Participants

From start of treatment through 30 days after completion of an estimated 4 months of neoadjuvant therapy

ID	Title	Description
OG000	Arm 1: PIK3CA Wild Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
OG001

Secondary

Number of Participants With a PEPI-0 Score

Preoperative endocrine prognostic index (PEPI) score is derived from four factors assigned a numerical score following neoadjuvant endocrine therapy, including Ki67 expression in the surgical specimen, pathologic tumor size (indicated as "T" below), lymph node status (indicated as "N" below), and estrogen receptor (ER) level (indicated as ER Allred below).
PEPI-0 score indicates T1 or T2, N0, Ki67 < 2.7%, ER Allred > 2.
It predicts a low risk of recurrence.

Some participants were not evaluable for this outcome measure due to participant withdrawal and surgery not completed.

Posted

Count of Participants

Participants

At the time of surgery (estimated to be 5 months)

ID	Title	Description
OG000	Arm 1: PIK3CA Wild Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Secondary

Change in Ki67 Level of Tumor Specimens

To assess Ki67 level on serially collected tumor specimens

Only participants who had tissue available at the two time points were evaluable for this outcome measure.

Posted

Mean

Full Range

percentage of Ki67 in tumor sample

Pre-treatment and cycle 1 day 15

ID	Title	Description
OG000	Arm 1: PIK3CA Wild Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
OG001	Arm 2: PIK3CA Mutant Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Secondary

Change in Ki67 Level of Tumor Specimens

To assess Ki67 level on serially collected tumor specimens

Only participants who had tissue available at the two time points were evaluable for this outcome measure.

Posted

Mean

Full Range

percentage of Ki67 in tumor sample

Cycle 1 day 15 and at time of surgery (approximately 2-4 weeks post completion of cycle 4 - each cycle is 28 days)

ID	Title	Description
OG000	Arm 1: PIK3CA Wild Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
OG001	Arm 2: PIK3CA Mutant Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Secondary

Number of Participants With Pathologic Complete Response (pCR)

-A pathologic complete response is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes.

Posted

Count of Participants

Participants

At the time of surgery (estimated to be 5 months)

ID	Title	Description
OG000	Arm 1: PIK3CA Wild Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
OG001	Arm 2: PIK3CA Mutant Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Secondary

Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event

Posted

Count of Participants

Participants

From start of adjuvant therapy through 30 days after completion of adjuvant therapy (estimated to be 2 years)

ID	Title	Description
OG000	Adjuvant Continuation	Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Units	Counts
Participants	OG000

Secondary

Overall Survival

Not Posted

5 years

Participants

Secondary

Relapse-free Survival

Not Posted

5 years

Participants

Secondary

Local Recurrence Rate

Local recurrence is defined as histologic evidence of ductal carcinoma in situ or invasive breast cancer in the ipsilateral breast or chest wall.

Not Posted

5 years

Participants

Secondary

Regional Recurrence Rate

Regional recurrence is defined as the cytologic or histologic evidence of disease in the ipsilateral internal mammary, ipsilateral supraclavicular, ipsilateral infraclavicular and/or ipsilateral axillary nodes or soft tissue of the ipsilateral axilla.

Not Posted

5 years

Participants

Secondary

Distant Recurrence Rate

Distant recurrence is defined as the cytologic, histologic, and/or radiographic evidence of disease in the skin, subcutaneous tissue, lymph nodes (other than local or regional metastasis), lung, bone narrow, central nervous system or histologic and/or radiographic evidence of skeletal or liver metastasis.

Not Posted

5 years

Participants

Secondary

Rate of Second Primary Breast Cancer

Second primary breast cancer is defined histologic evidence of ductal carcinoma in situ or invasive breast cancer in the contralateral breast or chest wall.

Not Posted

5 years

Participants

Secondary

Rate of Second Primary Cancer (Non-breast)

Second primary cancer (non-breast) is defined as any non-breast second primary cancer other than squamous or basal cell carcinoma of the skin, melanoma in situ, or carcinoma in situ of the cervix is to be reported and should be confirmed histologically whenever possible.

Not Posted

5 years

Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAE (4.0)	Systematic Assessment	EG0006 affected34 at risk EG0015 affected16 at risk EG0028 affected34 at risk EG0032 affected7 at risk
Palpitations	Cardiac disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0022 affected34 at risk EG003
Ear pain	Ear and labyrinth disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Blurred vision	Eye disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Dry eye	Eye disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Vision change	Eye disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Watering eyes	Eye disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Abdominal pain	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0011 affected16 at risk EG0021 affected34 at risk EG003
Bleeding gums	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Broken tooth	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Constipation	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0004 affected34 at risk EG0016 affected16 at risk EG0024 affected34 at risk EG003
Diarrhea	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0007 affected34 at risk EG0014 affected16 at risk EG0022 affected34 at risk EG003
Dry mouth	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0011 affected16 at risk EG0021 affected34 at risk EG003
Dyspepsia	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected34 at risk EG0012 affected16 at risk EG0021 affected34 at risk EG003
Flatulence	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0012 affected16 at risk EG0021 affected34 at risk EG003
Gastroesophageal reflux disease	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0011 affected16 at risk EG0021 affected34 at risk EG003
Gastrointestinal pain	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Hemorrhoidal hemorrhage	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Loose tooth	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Mucositis oral	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG00010 affected34 at risk EG0014 affected16 at risk EG0024 affected34 at risk EG003
Nausea	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG00011 affected34 at risk EG0015 affected16 at risk EG00211 affected34 at risk EG003
Oral pain	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Rectal pain	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Stomach cramping	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Stomatitis	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Toothache	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0022 affected34 at risk EG003
Vomiting	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected34 at risk EG0012 affected16 at risk EG0025 affected34 at risk EG003
Body aches	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Chills	General disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected34 at risk EG0011 affected16 at risk EG0022 affected34 at risk EG003
Cold symptoms	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Edema limbs	General disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Fat necrosis	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Fatigue	General disorders	CTCAE (4.0)	Systematic Assessment	EG00018 affected34 at risk EG00110 affected16 at risk EG00210 affected34 at risk EG003
Fever	General disorders	CTCAE (4.0)	Systematic Assessment	EG0004 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Flu like symptoms	General disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Localized edema	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0011 affected16 at risk EG0021 affected34 at risk EG003
Nose pain	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Pain	General disorders	CTCAE (4.0)	Systematic Assessment	EG0005 affected34 at risk EG0011 affected16 at risk EG0021 affected34 at risk EG003
Allergic reaction	Immune system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Shingles	Immune system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Axilla infection from surgery	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Cellulitis	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Eye infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Labia majora cyst	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Lung infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Oral yeast infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Sinusitis	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0012 affected16 at risk EG0020 affected34 at risk EG003
Thrush	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Tooth infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Upper respiratory infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Urinary tract infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0011 affected16 at risk EG0021 affected34 at risk EG003
Viral infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Wound infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Bruising	Injury, poisoning and procedural complications	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Hand wound	Injury, poisoning and procedural complications	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Seroma	Injury, poisoning and procedural complications	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Alanine aminotransferase increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0005 affected34 at risk EG0012 affected16 at risk EG0023 affected34 at risk EG003
Alkaline phosphatase increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0002 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Aspartate aminotransferase increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0005 affected34 at risk EG0010 affected16 at risk EG0023 affected34 at risk EG003
Cardiac troponin I increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Creatinine increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0013 affected16 at risk EG0023 affected34 at risk EG003
Lymphocyte count decreased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0004 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Neutrophil count decreased	Investigations	CTCAE (4.0)	Systematic Assessment	EG00021 affected34 at risk EG00110 affected16 at risk EG00225 affected34 at risk EG003
Platelet count decreased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0006 affected34 at risk EG0015 affected16 at risk EG0025 affected34 at risk EG003
Weight loss	Investigations	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
White blood cell decreased	Investigations	CTCAE (4.0)	Systematic Assessment	EG00026 affected34 at risk EG0018 affected16 at risk EG00214 affected34 at risk EG003
Anorexia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0004 affected34 at risk EG0013 affected16 at risk EG0021 affected34 at risk EG003
Hypercalcemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected34 at risk EG0011 affected16 at risk EG0021 affected34 at risk EG003
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected34 at risk EG0011 affected16 at risk EG0021 affected34 at risk EG003
Hyperkalemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0012 affected16 at risk EG0020 affected34 at risk EG003
Hypernatremia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Hypocalcemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Hypoglycemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Hypokalemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Hyponatremia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0007 affected34 at risk EG0015 affected16 at risk EG0022 affected34 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0004 affected34 at risk EG0012 affected16 at risk EG0022 affected34 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0006 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Osteoporosis	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0012 affected16 at risk EG0021 affected34 at risk EG003
Dizziness	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0007 affected34 at risk EG0012 affected16 at risk EG0022 affected34 at risk EG003
Dysgeusia	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Headache	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0009 affected34 at risk EG0012 affected16 at risk EG0026 affected34 at risk EG003
Memory impairment	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Middle ear inflammation	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Paresthesia	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Peripheral motor neuropathy	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected34 at risk EG0011 affected16 at risk EG0024 affected34 at risk EG003
Agitation	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Anxiety	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0004 affected34 at risk EG0012 affected16 at risk EG0021 affected34 at risk EG003
Confusion	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Depression	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected34 at risk EG0013 affected16 at risk EG0022 affected34 at risk EG003
Emotional changes	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Insomnia	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0007 affected34 at risk EG0014 affected16 at risk EG0024 affected34 at risk EG003
Acute kidney injury	Renal and urinary disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Urinary retention	Renal and urinary disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Breast pain	Reproductive system and breast disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected34 at risk EG0011 affected16 at risk EG0021 affected34 at risk EG003
Genital lump	Reproductive system and breast disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Pelvic pain	Reproductive system and breast disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Premature menopause	Reproductive system and breast disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0011 affected16 at risk EG0021 affected34 at risk EG003
Vaginal discharge	Reproductive system and breast disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Vaginal dryness	Reproductive system and breast disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Vasomotor symptoms	Reproductive system and breast disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0005 affected34 at risk EG0013 affected16 at risk EG0022 affected34 at risk EG003
Dry throat	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected34 at risk EG0014 affected16 at risk EG0023 affected34 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected34 at risk EG0011 affected16 at risk EG0022 affected34 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Postnasal drip	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Sinus disorder	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Sore throat	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0011 affected16 at risk EG0024 affected34 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected34 at risk EG0015 affected16 at risk EG0022 affected34 at risk EG003
Armpit pain	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Body odor	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Bullous dermatitis	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Dry fingertips	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected34 at risk EG0012 affected16 at risk EG0023 affected34 at risk EG003
Fever blister	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Heat rash	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected34 at risk EG0012 affected16 at risk EG0020 affected34 at risk EG003
Itching	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Macular lesion	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Palmar-plantar erythrodyesthesia syndrome	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0021 affected34 at risk EG003
Papulopustular rash	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected34 at risk EG0013 affected16 at risk EG0020 affected34 at risk EG003
Psoriasis	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Rash acneiform	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0011 affected16 at risk EG0021 affected34 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0004 affected34 at risk EG0011 affected16 at risk EG0021 affected34 at risk EG003
Hot flashes	Vascular disorders	CTCAE (4.0)	Systematic Assessment	EG00013 affected34 at risk EG0019 affected16 at risk EG0026 affected34 at risk EG003
Hypertension	Vascular disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0011 affected16 at risk EG0020 affected34 at risk EG003
Lymphedema	Vascular disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Superficial throbophlebitis	Vascular disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Gastritis	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003
Hiatal hernia	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected34 at risk EG0010 affected16 at risk EG0020 affected34 at risk EG003

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
C500026	palbociclib
D000077384	Anastrozole
D017273	Goserelin
D013514	Surgical Procedures, Operative
D059039	Standard of Care

ID	Term
D009570	Nitriles
D009930	Organic Chemicals
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D007987	Gonadotropin-Releasing Hormone
D010906	Pituitary Hormone-Releasing Hormones
D007028	Hypothalamic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D009479	Neuropeptides
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D009842	Oligopeptides
D009419	Nerve Tissue Proteins
D011506	Proteins
D019984	Quality Indicators, Health Care
D011787	Quality of Health Care
D006298	Health Services Administration
D017530	Health Care Quality, Access, and Evaluation

ID	Title	Description
BG000	Arm 1: PIK3CA Wild Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
BG001	Arm 2: PIK3CA Mutant Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
BG002	Arm 3: Endocrine Resistant Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm 1: PIK3CA Wild Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.	0	34	2	34	34	34
EG001	Arm 2: PIK3CA Mutant Type Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.	0	16	1	16	16	16
EG002	Arm 3: Endocrine Resistant Cohort	Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.	4	34	1	34	34	34
EG003	Adjuvant Continuation	Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.	0	7	1	7	7	7