1.0) Pt. must have achieved a CR or PR after 1 prior chemo and/or RT Tx.
2.0) Pt. with limited stage SCLC must be randomized 3-12 wks from last dose of chemo, and when relevant > 2wks from RT.
3.0) Pt. with extensive stage SCLC must be randomized 3-6 wks from last dose of chemo.
4.0) Life expectancy >/= 12 weeks.

***SJMH will NOT be participating in this study***

*Credentialing required. Please check your site's credentialing status.*
CURRENT SITES CREDENTIALED:
Genesys, Oakland, St. Alphonsus, St. John

*Check for eligibility to DCP-001*
-Patients must be female.
-Pathologically confirmed diagnosis of breast cancer, clinical stage I-II (T1-3 N0 M0, T0-2 N1 M0).
-Diagnosis must be by needle biopsy; patients diagnosed by surgical excision are excluded
-Patients must have ER and PR negative breast cancer
-No patients with previous ipsilateral invasive breast cancer or DCIS
-No patients with bilateral breast cancer
-No patients with known deleterious mutations in breast cancer (BRCA) genes
-No current history of receiving hormonal therapy, tamoxifen, and or aromatase inhibitors for therapeutic measures
-No history of chemotherapy for cancer within 6 months prior to registration
-No patients scheduled to receive partial breast irradiation following breast conserving surgery
-Patients must be eligible for breast conserving therapy
-Patients must be suitable to undergo MRI
-No prior MRI of study breast within the 12 months prior to registration
-No history of breast biopsy (including FNA) of the study breast within 6 months prior to the MRI

-Neoadjuvant chemotherapy patients are allowed

-Pathologic confirmation of invasive breast cancer diagnosed by core needle biopsy
-Clinical T2-T4c, any N, M0 invasive breast cancer with the goal being surgery to complete excision of the tumor in the breast and the lymph node.
-The extent of disease is a solitary lesion where the lesion is palpable, can be measured bidimensionally, and largest diameter is at least 2cm.
-Patients with contralateral ductal carcinoma in situ and/or invasive breast cancer are NOT eligible.

-Patients with multi-focal breast cancer (defined as more than one lesion of invasive breast cancer in the same breast separated from the dominant breast lesion by less than 5 cm of radiologically normal breast tissue) are eligible.

-Disease must be ER positive
-Disease must be HER2 negative
-ECOG PS 0-2
-Patients must be postmenopausal
-No prior treatment for this cancer including surgery, radiation therapy, chemotherapy, biotherapy, hormonal therapy or investigational agent prior to study entry.

**Effective 09/01/2020,  Step 2 (Confirmation of Evaluability) registration is temporarily unavailable for new registrations**

*Credentials required. Please check your site's credentialing status.*
CURRENT SITES CREDENTIALED:
SJMH-(A2, Canton only), Livonia, Genesys Hurley, St. Alphonsus, Oakwood, St. John Hospital, Oakland, Macomb, St. Mays Saginaw, Holy Cross, Sparrow

*Patients may simultaneously enroll to BWEL A011401, if eligible.

Pre-Registration Eligibility Criteria:
-Clinical stage T1-3 N1 M0 breast cancer at diagnosis (prior to the start of neoadjuvant chemotherapy)
-No inflammatory breast cancer
-All patients must have had an axillary ultrasound with fine needle aspiration (FNA) or core needle biopsy of axillary lymph nodes documenting axillary metastasis at the time of diagnosis, prior to neoadjuvant chemotherapy.
-Patients must have completed at least 6 cycles of neoadjuvant chemotherapy consisting of an anthracycline and/or taxane-based regimen without evidence of disease progression in the breast or the lymph nodes.
-Patients must have completed all planned chemotherapy prior to surgery. Sandwich chemotherapy is not allowed (i.e. chemotherapy planned to be given after surgery).
-Patients with HER-2 positive tumors must have received neoadjuvant trastuzumab or other approved anti-HER-2 therapy
-All patients must have a clinically negative axilla (no palpable lymph nodes or bulky adenopathy) on physical examination documented at the completion of neoadjuvant chemotherapy.
-No more than 8 weeks of neoadjuvant endocrine therapy prior to the start of neoadjuvant chemo.
-No neoadjuvant radiation therapy.
-No sentinel lymph node (SLN) surgery/excisional biopsy for pathological confirmation of axillary status prior to or during neoadjuvant chemotherapy.
-No prior ipsilateral axillary surgery, such as excisional biopsy of lymph node(s) or treatment of hidradenitis.
-ECOG PS 0-1

Post-Operative Eligibility Criteria: [For cases where ALND has not been performed and one of the following is true:  --intra-operative evaluation of sentinel lymph node could not be/was not performed and final pathology identified a positive SLN with metastasis greater than 0.2 mm OR --sentinel lymph node on intra-operative evaluation considered negative was found to be positive on final pathology (with metastasis greater than 0.2 mm).]
-Breast surgery (lumpectomy or mastectomy) and sentinel lymph node surgery must be completed within 56 days of the completion of neoadjuvant chemotherapy.
-Among the minimum of 2 and the maximum of 6 sentinel nodes identified and excised by the surgeon, no more than 8 lymph nodes (sentinel and non-sentinel) were found by the pathologists to have been actually excised.
-For those patients who also undergo contralateral breast surgery, if invasive disease is found in the contralateral breast, the patient is not eligible for registration /randomization. 

Pre-registration Eligibility:
-Women who agree to undergo a standard of care core biopsy of recurrent or metastatic breast cancer to confirm that is ER+ and HER2 negative
-Patient must have been previously treated with an aromatase inhibitor either in the adjuvant or metastatic setting, and have primary or secondary endocrine resistant disease defined as follows--

Primary clinical resistance:
--Recurrence within the first 2 years of adjuvant endocrine therapy while on endocrine therapy OR 
--Progression within first 6 months of initiating first-line endocrine therapy for the treatment of metastatic breast cancer (while on endocrine therapy);

Secondary clinical resistance:
--Recurrence during years 2-5 of adjuvant endocrine therapy (or within 12 months of completing adjuvant endocrine therapy OR
--Progression occurring 6 or more months after initiating endocrine therapy for metastatic disease while on endocrine therapy
-Must have history of measurable disease 
-No history of visceral crisis, lymphangitic spread or known brain metastases.
-Women must be postmenopausal
-No more than two prior chemotherapy regimens in the metastatic setting.
-Prior treatment with an aromatase inhibitor (either anastrozole, letrozole or exemestane), either in the adjuvant or metastatic setting is required.
-Unlimited prior endocrine regimens in the metastatic setting, which may have included an everolimus containing regimen.
-Prior tamoxifen treatment is allowed in the adjuvant setting, but patients must not have experienced relapse within 1 year of stopping tamoxifen.
-No prior treatment with tamoxifen in the metastatic setting.
-ECOG PS 0-2  

Registration Eligibility:
-Must have measurable disease or bone only disease 
-No visceral crisis, lymphangitic spread or known brain metastases. 
-Histologic confirmation from pre-registration that locally advanced or metastatic breast cancer is estrogen receptor positive and HER2 negative.
-None of the following therapies are allowed within 2 weeks prior to registration: chemotherapy, immunotherapy, biologic therapy, hormonal therapy, monoclonal antibodies, radiation therapy, anti-HER2 or other targeted therapy. 

***Patients must not have metastatic breast cancer***

*Effective 07/06/17 Sub-study HO1 is Closed to Accrual.

*Effective 02/01/2021, Step 1 is Closed to Accrual.  

*Effective 03/25/2021, Step 2 patient randomization is Closed to Accrual. 
*Check for eligibility to DCP-001*

-Subjects must have histologically confirmed invasive breast cancer with diagnosis within the past 12mo.
--Neoadjuvant subjects should have no evidence of clinical T4 disease prior to chemo and surgery.
--Bilateral disease is allowed provided diagnoses are synchronous
-Must be HER-2 negative
-Eligible TNM stages include:
--ER and PR negative for T2 or T3 N0, T0-3N1-3
--ER and/or PR positive for T0-3N1-3 or T3N0
-All adjuvant or neoadjuvant chemo and surgery must be completed at least 21 days prior to registration
-Surgical margins must be clear
-All subjects must have sentinel lymph node biopsy and/or axillary lymph node dissection
-All women who undergo breast conserving therapy must receive concomitant radiotherapy. RT can be administered prior to or during protocol treatment.
-Patients with hormone receptor positive disease must receive at least 5 years of adjuvant hormonal therapy initiated prior to or during protocol treatment.
-ECOG PS must be 0-1.
-No history of comorbid conditions that preclude moderate physical activity.
-Must not have had bariatric surgery or plan to in the next 2 years.
-BMI must be greater than or equal to 27 kg/m2 within 56 days prior to registration.
-Must have self-reported ability to walk at least 2 blocks.
-Must not be participating in another weight loss, physical activity or dietary intervention clinical trial. Subjects may co-enroll in pharmacologic therapy trials.
-Must be able to read and comprehend English.

**As of 2/15/17, per on-study guidelines, patients should not be planning to undergo a major surgical procedure (e.g. hysterectomy) within 3 months after study registration.  (Breast reconstruction is allowed during study participation)**

*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status.
CURRENT SITES CREDENTIALED: SJMH TH Ann Arbor, Canton, Chelsea, Brighton, and Livonia, Genesys, Hurley, Lehigh Valley

Eligibility Criteria:

A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

3.2.1 Age ≥ 18 years

3.2.2 ECOG Performance Status 0-2

3.2.3 Triple Negative Breast Cancer

3.2.3.1 Patients with a history of stage T1cN1-2 or T2-4N0-2 breast cancer according to the primary tumor-regional lymph node anatomic staging criteria of the American Joint Committee on Cancer (AJCC), 8th edition as determined by the investigator in radiologic assessment, clinical assessment or both.

3.2.3.2 Patients must have no residual invasive disease in the breast or lymph nodes after the completion of neoadjuvant therapy. Residual DCIS is allowed. Isolated tumor cells are considered node negative.

3.2.3.3 ER and PR ≤10%; HER2-negative by ASCO/CAP guidelines (IHC and FISH)

3.2.3.4 If invasive disease was present in both breasts, participation in the study is permitted as long as the eligibility criteria are met for both tumors/breasts 

3.2.4 Prior Treatment

3.2.4.1 Patients must have received neoadjuvant chemotherapy in combination with pembrolizumab for a minimum of 6 cycles. All systemic chemotherapy must have been completed preoperatively.

3.2.4.2 An interval of no more than 12 weeks between the completion date of the final surgery and the date of randomization. Note: Adjuvant radiation can be given on study. If given, it is encouraged to be given concurrently with pembrolizumab, per investigator discretion. Treatment with adjuvant pembrolizumab is strongly discouraged prior to participation in this trial, but if administered (e.g., if patients are awaiting pathology results), pembrolizumab may be administered for up to 6 weeks post-surgery and must be completed prior to registration.

3.2.4.3 Use of investigational anti-cancer agents must be discontinued at time of registration.  

3.2.4.4 Adequate excision: Surgical removal of all clinically evident disease in the breast and lymph nodes as follows:

Breast surgery: Total mastectomy or breast-conserving surgery with histologically negative margins, including no ink on tumor for DCIS, at the time of excision.

For patients who undergo breast-conserving surgery, the margins of the resected specimen must be histologically free of ductal carcinoma in-situ (DCIS) as determined by the local pathologist. If pathologic examination demonstrates DCIS at the line of resection, additional operative procedures may be performed to obtain clear margins. If DCIS is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible. Patients with margins positive for classic lobular carcinoma in situ (LCIS) are eligible without additional resection. 

Lymph node surgery: 

For a patient with clinically N0 disease, a sentinel lymph node biopsy should have been performed at time of surgical evaluation, and if pathologically node positive, the patient is no longer eligible. Isolated tumor cells are considered node-negative.

For a patient with clinically N1 disease at diagnosis (with positive results from a fine-needle aspiration, core biopsy, or sentinel node biopsy performed prior to preoperative therapy) additional surgical evaluation of the axilla following preoperative therapy is required. 

**PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST** 

*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status.

CURRENT SITES CREDENTIALED: Trinity Health IHA (Brighton, Ann Arbor, Canton, Chelsea), Livonia, Genesys

Eligibility Criteria:

3.2.1 Unilateral invasive adenocarcinoma of the breast that is histologically confirmed

3.2.1.1 Invasive breast cancer is estrogen receptor positive in ≥10% of cells

3.2.1.2 HER2 negative by current ASCO/CAP guidelines

3.2.2 The patient must have a multigene assay with a low-risk score, including any of the following (if more than one genomic assay was obtained, both are required to be low-risk): 

• Oncotype DX Recurrence Score ≤ 25

• Mamma Print low risk  

• Prosigna Risk of Recurrence ≤40 

3.2.3 Surgical pathology requirements:

3.2.3.1 Tumor size must be ≤3 cm by pathologic evaluation.

3.2.3.2 Adequate surgical removal of all clinically evident disease in the breast with either breast conserving surgery or mastectomy. Negative margins on final pathology are required. Additional excisions may be performed to obtain clear margins before registration.

3.2.3.3 No clinical (cN1, cN2, cN3) or pathologic (pN1mi, pN1, pN2, or pN3) evidence of lymph node involvement on either needle biopsy or surgical lymph node assessment. Patients with pN0(i+) or pN0 (mol+) are eligible. 

o Surgical axillary staging (sentinel lymph node biopsy ± axillary lymph node dissection) is completed according to physician discretion.

o For patients with negative preoperative axillary ultrasonography, clinicians may selectively choose to forego surgical axillary staging. Ipsilateral axillary ultrasound showing no lymph node involvement with no evidence of lymphadenopathy or suspicious thickening is required in this scenario. 

3.2.4 No tumors that are considered pT4

3.2.5 No definitive clinical or radiologic evidence of metastatic disease

3.2.6 No palpable or radiographically suspicious axillary, supraclavicular, infraclavicular, or internal mammary lymph nodes, unless there is histologic confirmation that these lymph nodes are negative for tumor 

3.2.7 No suspicious microcalcifications, densities, or palpable abnormalities in the ipsilateral or contralateral breast, unless biopsied and found to be benign

3.2.8 An interval of no more than 20 weeks between the date of surgery and the date of registration. 3.2.9 Must have had a bilateral mammogram or MRI within 6 months prior to registration. 

3.2.10 Must be intending to take endocrine therapy for at least 5 years duration 

3.2.11 Prior Treatment

3.2.11.1 No prior treatment with endocrine therapy or chemotherapy for the currently diagnosed breast cancer prior to registration. (Short course endocrine therapy of ≤ 6 weeks duration is acceptable after core biopsy and before surgery, if genomic testing is assessed on the biopsy core and meets eligibility requirements for a low-risk score.)

3.2.11.2 No use of oral hormone replacement therapy within 7 days prior to registration.  

3.2.12 Age ≥ 18 years and female 

3.2.13 ECOG Performance Status ≤ 2 

3.2.14 Postmenopausal status confirmed as meeting one of the following:

• No spontaneous menses ≥1 year or

• No menses for <1 year with FSH and estradiol levels within a postmenopausal range according to institutional standards or

• Previous bilateral surgical oophorectomy 

**PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST**