The research study procedures include screening for eligibility and study treatment including
laboratory evaluations, physical exams, questionnaires, and follow up visits.
- Participants will receive HER2-directed treatment for 1 year and hormonal therapy for
approximately 5 years.
- It is expected that about 375 people will take part in this research study.
This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational drug combination to learn whether the drug works in
treating a specific disease. "Investigational" means that the drug combination is being
The drugs trastuzumab and pertuzumab are both monoclonal antibodies, which are
disease-fighting proteins made by cloned immune cells. The U.S. Food and Drug Administration
(FDA) has approved trastuzumab, pertuzumab, and trastuzumab + pertuzumab subcutaneous fixed
dose combination (PHESGO) as treatment for HER2 positive breast cancer. The FDA has also
approved hormonal therapies as treatment for hormone receptor positive breast cancer.
- HER2-positive T1 histologically confirmed invasive carcinoma of the breast. Patients
must have node-negative (N0) or micrometastases (N1mi) breast cancer according to the
AJCC 8th edition anatomic staging table.
- If the patient has had a negative sentinel node biopsy, then no further axillary
dissection is required, and the patient is determined to be node-negative.
Axillary nodes with single cells or tumor clusters ≤ 0.2 mm by either H&E or
immunohistochemistry (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. An axillary
dissection is not required to be performed in patients with a micrometastasis
found by sentinel node evaluation. In cases where the specific pathologic size of
lymph node involvement is subject to interpretation, the overall principal
investigator will make the final determination as to eligibility. The
investigator must document approval in the patient medical record.
- Patients who have an area of T1aN0, ER+ (defined as ≥ 10%), HER2-negative cancer
in either breast, in addition to their primary HER2 positive tumor, are eligible.
- For unifocal disease, all invasive disease must have been tested for ER and PR (for
multifocal disease, see below). Either ER or PR must be positive, defined as ER ≥10%
or PR ≥10%. ER- and PR-assays should be performed by immunohistochemical methods
according to the local institution standard protocol.
- HER2-positive by ASCO CAP 2018 guidelines, confirmed by central testing. See Appendix
I for ASCO CAP 2018 HER2 testing guidelines.
- NOTE: DCIS components will not be counted in the determination of HER2 status
- NOTE: HER-2 status must be confirmed to be positive by central review prior to
patient starting protocol therapy. Patients previously having had HER2 testing by
NeoGenomics do not need to undergo retesting for central confirmation of HER2
status. A pathology report documenting testing by NeoGenomics should be provided
at time of patient registration.
- Bilateral breast cancers that individually meet eligibility criteria are allowed.
- Patients with multifocal or multicentric disease are eligible as long as each tumor
individually meets eligibility criteria, with the following exceptions: (1) central
confirmation of HER2 status is needed only for any site of disease that is tested to
be HER2-positive by local testing (unless original testing was done by NeoGenomics);
(2) all areas that were locally tested for ER and PR status must be ER/PR positive (as
- Patients with a history of ipsilateral DCIS are eligible as long as the patient has
not received prior hormonal therapy. Patients with a history of contralateral DCIS are
- ≤ 90 days between the date of protocol registration and the patient's most recent
breast surgery for this breast cancer
- Patients must have undergone definitive breast surgery for the current malignancy. All
tumor should be removed by either a modified radical mastectomy or a segmental
mastectomy (lumpectomy), with either a sentinel node biopsy or axillary dissection
-- All 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. Radiation therapy to the conserved
breast is required.
- May have received up to 8 weeks of hormonal therapy as adjuvant treatment for this
cancer. Patients should otherwise not have received prior hormonal therapy.
- Prior oophorectomy (including for cancer therapy) is allowed.
- Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have any
contraindications to radiation therapy.
- Patients who have participated in a window study (treatment with an investigational
agent prior to surgery for ≤2 weeks) are eligible. Patients must have discontinued the
investigational agent at least 14 days before participation.
- Men and women with any menopausal status ≥18 years of age
- ECOG Performance Status 0 or 1
- Participants must have normal organ and marrow function as defined below:
- ANC ≥ 1000/mm3
- hemoglobin ≥8 g/dl
- platelets ≥ 75,000/mm3
- AST and ALT both <5x institutional ULN
- Total bilirubin ≤ 1.5 mg/dL. For patients with Gilbert syndrome, the direct
bilirubin should be <institutional ULN
- Serum creatinine ≤ 2.0 mg/dL OR calculated GFR ≥ 30mL/min
- Left ventricular ejection fraction (LVEF) ≥ 50%
- Post-menopausal patients must meet one of the following criteria:
- Prior bilateral ovariectomy/oophorectomy
- Age ≥ 60 years
- Age < 60 years with intact uterus and amenorrhoeic for ≥ 12 consecutive months
prior to chemotherapy and/or endocrine therapy exposure (medication-induced
amenorrhea is not acceptable to meet this criterion)
- Age < 60 years hysterectomized and FSH and plasma estradiol levels in the
postmenopausal range according to local policies prior to chemotherapy and/or
endocrine therapy exposure.
- Willingness to discontinue contraceptive hormonal therapy, e.g. birth control pills,
prior to registration and while on study
- Premenopausal patients must have a negative serum or urine pregnancy test, including
women who have had a tubal ligation and women less than 12 months from their last
- Women of childbearing potential and men with partners of childbearing potential must
be willing to use one highly effective form of nonhormonal contraception or two
effective forms of nonhormonal contraception by the patient and/or partner and
continue its use for the duration of the study treatment and for 7 months after the
last dose of antibody treatment and 3 months after the last dose of hormonal
- Patients must be willing and able to sign informed consent.
- Patients must be willing to provide archival tissue for research purposes.
- If patient is English-speaking, must be willing to fill out patient questionnaires.
- Neoadjuvant or adjuvant chemotherapy for this breast cancer prior to enrollment is
- Any of the following due to teratogenic potential of the study drugs:
- Pregnant women
- Nursing women
- Women of childbearing potential who are unwilling to employ adequate
contraception (condoms, diaphragms, IUDS, surgical sterilization, abstinence,
etc). Hormonal birth control methods are not permitted.
- Men who are unwilling to employ adequate contraception (condoms, surgical
sterilization, abstinence, etc).
- Participants who are receiving any other investigational agents for treatment of
breast cancer, unless specific approval is obtained from the Sponsor-Investigator.
- Locally advanced tumors at diagnosis, including tumors fixed to the chest wall, peau
d'orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawny
cutaneous induration with an erysipeloid edge)
- Patients with a history of previous invasive breast cancer.
- Individuals with a history of a different malignancy are ineligible except for the
- Individuals with a history of other malignancies are eligible if they have been
disease-free for at least 5 years and are deemed by the investigator to be at low
risk for recurrence of that malignancy.
- individuals with the following cancer are eligible regardless of when they were
diagnosed and treated: cervical cancer in situ, and non-melanoma cancer of the
- Intercurrent illness including, but not limited to: ongoing or active, unresolved
systemic infection, renal failure requiring dialysis, active cardiac disease, prior
myocardial infarction (asymptomatic changes on EKG suggestive of old MI is not an
exclusion), history of CHF, current use of any therapy specifically for CHF,
uncontrolled hypertension, significant psychiatric illness, or other conditions that
in the opinion of the investigator limit compliance with study requirements.