Exposure to radiation can impact immune cells that are present in the blood, such as lymphocytes. It is hypothesized that larger radiation fields and/or longer courses of radiation, result in greater decrease in immune cells. To test this hypothesis, investigators will take blood samples from subjects undergoing two different standard of care radiation regimens for prostate cancer, and subjects undergoing two different standard of care regimens for breast cancer.

The study prospectively collects blood specimens for assessment of peripheral immune mediators in 4 distinct clinical settings of standard radiotherapy. In addition to collecting blood specimens, the study will also collect physical and dosimetric information of treatment such as total dose, number of treatments, and/or size of the radiation targe, as these will allow the investigators to study the impact of radiation variables on the immune system. Stool specimens will be collected at baseline, end of radiation therapy and during the follow up visit to detect microbiome changes associated with different radiation treatment at various time points. Humans are colonized by commensal bacteria, which outnumber human cells. These normal bacteria colonize mucosal surfaces and play a critical role in immunity. It is hypothesized that the underlying microbiota may also undergo changes in composition that correspond to the regimen of radiation that is utilized. By collecting stool specimens, investigators will be able to study microbial changes and how these changes correlate with alteration in immune mediators (i.e., lymphocytes, cytokines) present in blood samples before, during and after radiation; and explore the association between these parameters and type of radiation received.

Cohort 1a and b: Prostate cancer subjects undergoing 9 week radiation

Inclusion criteria:

• Biopsy-proven diagnosis of prostate adenocarcinoma
• Age ≥ 18

Exclusion criteria:

• History of prior pelvic radiation (external beam or brachytherapy)
• Prior or concurrent lymphomatous/hematogenous malignancy, or history of prior/concurrent invasive malignancy during the past 5 years
• History of hormone therapy such as LHRH agonists (gosrelin, leuprolide), anti-androgens (flutamide, bicalutamide), surgical castration (orchiectomy)
• History of irritable bowel disease
• Evidence of lymph node involvement or metastatic disease

Cohort 2a : Breast cancer subjects undergoing standard fractionation RT of 5 weeks

Inclusion criteria:

• Biopsy-proven diagnosis of invasive breast cancer, s/p breast surgery to negative margins, and requiring adjuvant breast and nodal RT
• Age ≥ 18

Exclusion criteria:

• History of prior radiation therapy to the ipsilateral breast
• Prior or concurrent lymphomatous/hematogenous malignancy, or history of prior/concurrent invasive malignancy during the past 5 years
• < 1 month from completion of chemotherapy to start of RT
• Evidence of metastatic disease

Cohort 2b: Breast cancer subjects undergoing PBI

Inclusion criteria:

• Post-menopausal women defined as either 1) at least 2 years without menstrual period or 2) or patients older than 50 with serological evidence of post-menopausal status or 3) hysterectomized patients of any age with FSH confirmation of post-menopausal status.
• Post-segmental mastectomy with negative margins
• If bilateral, pT1 breast cancer, excised with negative margins AND/OR
• pTis excised with negative margins
• Clinically N0 or pN0 or sentinel node negative
• Diagnosis of ductal carcinoma in situ DCIS, limited to <2cm size of DCIS and to lesions of low or intermediate grade, excised (or re-excised) with final negative margins ( no DCIS on inked margins).
• Age ≥ 18

Exclusion criteria:

• History of prior radiation therapy to the ipsilateral breast
• Presence of a proportion of DCIS in the core biopsy specimen which is compatible with extensive intraductal component (EIC).
• < 1 month from completion of chemotherapy to start of RT
• Evidence of metastatic disease

Men with biopsy-proven, non-metastatic prostate adenocarcinoma, meeting the inclusion/exclusion criteria below, and electing to undergo definitive radiation treatment, will be eligible for participation.

Women with biopsy-proven, non-metastatic invasive or in situ breast cancer meeting the inclusion/exclusion criteria below will be eligible for participation.