Endocrine Therapy in Treating Patients With HER2 Negative, Low Risk Breast Cancer

PRIMARY OBJECTIVES:

I. To estimate the conversion rate from a standard low-toxicity approach to
guideline-directed therapy which includes surgery +/- radiation therapy as a result of
progression of disease or patient/provider choice.

II. To examine factors that might differ between those who convert from the low-toxicity
approach to the guideline-directed therapy and those do not convert.

SECONDARY OBJECTIVES:

I. To measure the safety and clinical effectiveness of systemic endocrine therapy used in a
prolonged neoadjuvant fashion.

II. To evaluate the impact of risk-stratified care in Quality-Adjusted Life Years (QALY) and
QALY gains.

III. To estimate the cost savings of indefinitely delaying surgery and radiation in favor of
systemic endocrine therapy alone.

OUTLINE:

Patients receive exemestane orally (PO) once daily (QD), anastrozole PO QD, letrozole PO QD,
tamoxifen citrate PO QD, or toremifene citrate PO QD at the discretion of the treating
physician. Treatment continues in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

- Able to provide written informed consent

- A diagnosis of invasive breast cancer, with or without an in situ component, that is:

- Originally identified by screening mammography

- Characterized by standard diagnostic mammography +/- breast ultrasound

- Clinically node negative

- Confirmed by breast magnetic resonance imaging (MRI) in a facility that maintains
active American College of Radiology (ACR) accreditation to be of low clinical
stage (=< 2 cm, node negative, unifocal invasive)

- Estrogen receptor (ER) and progesterone receptor (PR) Allred scored, each > 5/8

- Her2 negative using American Society of Clinical Oncology (ASCO)-College of
American Pathologists (CAP) guidelines

- ki‐67 proliferation scored, < 20%

- Clinical Nottingham grade 1 or 2

- Scored on the MammaPrint 70-gene breast cancer recurrence assay as low risk

- Prior to the discovery of the breast cancer, clinically post‐menopausal as defined as:
i) one or more years from last menses; or ii) history of oophorectomy; or iii)
follicle stimulating hormone (FSH) test result in the post-menopause reference range

- Willing to accept oral endocrine therapy with a third generation aromatase inhibitor
(AI) or selective estrogen receptor modifier (SERM)

- Willing to undergo routine surveillance with breast ultrasound and/or mammography

Exclusion Criteria:

- Known contraindication to aromatase inhibitor or SERM therapy

- Pregnant at time of or within prior year of diagnosis

- Clinically detected or palpable disease prior to biopsy in either breast or
ipsilateral axilla

- Prior history of invasive breast cancer or ductal breast carcinoma in situ (DCIS)

- Prior use of aromatase inhibitor therapy apart from assisted reproduction

- Prior use of SERM

- Unmanaged/uncontrolled mental health disorder

- Life expectancy < 6 months (m) for any cause

- Biopsy confirmed multifocal, multicentric, or contralateral disease that is invasive
or non-invasive

- DCIS with focal invasion