ATOP TRIAL: T-DM1 in HER2 Positive Breast Cancer

Inclusion Criteria

• •Participants must have histologically or cytologically confirmed HER2-positive disease by local pathology, defined as immunohistochemistry (IHC) 3+ or amplification by FISH (HER2/CEP17 ratio ≥2 or an average of ≥6 HER2 gene copies per nucleus) AND confirmed by Central Pathology Review (Dr. Deborah Dillon at Brigham and Women's Hospital, Boston, MA) prior to patient being registered to begin protocol therapy. See section 3.4. http://ascopubs.org/doi/full/10.1200/jco.2013.50.9984
• •NOTE: DCIS components should not be counted in the determination of HER2 status.
• •Age ≥60 years at the time of study registration (men and women eligible)
• •Participants must have histologically or cytologically confirmed Stage I-III breast cancer with the following criteria met:
• •If node-negative or if node status unknown (because it was not assessed), tumor must be \>5 mm of any hormone receptor subtype (document ER/PR status: if some ER/PR staining is present, ER and PR negative are defined as being positive in \<10% cells \[per local pathology read\]).
• •If node-positive (N1-N3), T1mi, T1a, T1b, T1c, T2, or T3 tumors are eligible (see below for further details on defining node-negative disease) Definition of node-negative disease (when node status known): If the patient has had a negative sentinel node biopsy and/or a negative axillary dissection, then the patient is determined to be node-negative. Axillary nodes with single cells or tumor clusters ≤ 0.2 mm by either H\&E or IHC will be considered node-negative. Any axillary lymph node with tumor clusters between 0.02 and 0.2cm is considered a micrometastasis. Patients with a micrometastasis are eligible even if their tumor is \</= 5mm. An axillary dissection is not required to be performed in patients with a positive sentinel node and management of the axilla will be left up to the treating provider. In cases where the specific pathologic size of lymph node involvement is subject to interpretation, the principal investigator will make the final determination as to eligibility. In these special situations, the investigator must document this approval in the patient medical record.
• •ER/PR determination assays performed by IHC methods according to the local institution standard protocol.
• •Standard chemotherapy/trastuzumab declined by patient OR patient is deemed by physician for any reason to not be a candidate for standard therapy (i.e. patient and/or provider choose not to pursue standard trastuzumab-based chemotherapy regimen because of concerns related to toxicity or provider/patient preference).
• •All tumor removed by either a modified radical mastectomy or a segmental mastectomy (lumpectomy).
• •NOTE: Management of axillary lymph nodes is up to the treating provider; however, all surgical margins should be clear of invasive cancer or DCIS (i.e., no tumor on ink). The local pathologist must document negative margins of resection in the pathology report. If all other margins are clear, a positive posterior (deep) margin is permitted, provided the surgeon documents that the excision was performed down to the pectoral fascia and all tumor has been removed. Likewise, if all other margins are clear, a positive anterior (superficial; abutting skin) margin is permitted provided the surgeon documents that all tumor has been removed.
• •-≤90 days from the patient's most recent breast surgery for this breast cancer. Note: In cases where registration will occur \>90 days from surgery but within an acceptable time frame, patient may be eligible for enrollment with approval from the PI, Rachel Freedman MD, MPH.
• •ECOG Performance Status (PS) 0-2. See Appendix F.
• •Baseline ejection fraction ≥50% by MUGA scan or echocardiogram performed ≤60 days prior to registration.
• •The following laboratory values obtained ≤14 days prior to registration:
• •* Absolute neutrophil count (ANC) ≥1500/mm3
• •* Platelet count ≥100,000/mm3
• •* Hemoglobin \>9.0 g/dL
• •* Total bilirubin ≤1.5 x upper limit of normal (ULN). If patient has known Gilbert's syndrome, the suggested threshold for treatment is a total bilirubin ≤2.0 x ULN, but will be left to the treating providers discretion.
• •* AST and ALT ≤2.5 x ULN, alkaline phosphatase ≤2.5 x ULN
• •* INR \<1.5 x ULN for institution unless patient is on planned therapy with anticoagulants (i.e., warfarin) with higher target planned. In those cases, INR up to 3.5 is acceptable.
• •* PTT \<1.5 x ULN for institution unless patient is on planned therapy with heparin or heparin-like products Note: In the case of longstanding ethnic neutropenia, patient may be eligible for enrollment with approval from the PI, Rachel Freedman MD, MPH.
• •Life expectancy \>5 years per provider's assessment
• •Willing to employ adequate and appropriate birth control if applicable
• •NOTE: This study is for patients aged 60 and older, and most female patients will have entered menopause by this time; however patients should not become pregnant while on this study because T-DM1 can affect an unborn baby. Pre-menopausal women need to use birth control while on this study and women should not breastfeed a baby while on this study. Any man treated on this study will also need to use contraception if his partner is a premenopausal female. Patients should check with their health care provider about what kind of birth control methods to use and how long to use them.
• •Negative urine or serum pregnancy test done ≤7 days prior to registration, for women of childbearing potential only
• •NOTE: In the rare case that a woman enrolling on study is of childbearing potential, a pregnancy test is required prior to enrollment on study.
• •Able to provide informed written consent.
• •Willing to return to consenting institution for follow-up at 6 months
• •Willing to provide blood samples for mandatory correlative research purposes.
• •Ability to understand and the willingness to sign a written informed consent document