Effect of HSD3B1 (1245C) Gene Mutation on Treatment of Stage I-III Breast Cancer

Inclusion Criteria:

* Subject must be female age \>= 18 years.
* Postmenopausal as defined by at least one of the following:

  * Age \>= 60 years;
  * Age \< 60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; or serum estradiol and follicle stimulating hormone levels within the local laboratory's normal reference range for postmenopausal females;
  * Documented bilateral oophorectomy.
* Histologically confirmed diagnosis of carcinoma of the breast, clinical stage I-III.
* Minimum tumor diameter of 1.0 cm as assessed by palpation or imaging (e.g., ultrasound) and with enough tumor left after the initial diagnostic biopsy to provide tumor tissue during the planned tumor resection.
* Candidate for surgical resection.
* ER+ breast cancer (\> 1% positive stained cells) based on the most recent tumor biopsy documented by a local laboratory or medical record.
* Ki67 \>= 10%.
* HER2-negative breast cancer based on the most recent tumor biopsy and documented by a local laboratory or medical record. HER2-negative tumor is defined per American Society of Clinical Oncology and the College of American Pathologists guidelines, 2018.
* Stated willingness to comply with all study procedures and availability for the duration of the study.
* Prior use of hormone contraceptives and replacement therapy is allowed (e.g., estrogen and/or progestin) if discontinued \> 6 months prior to diagnosis. Vaginal preparations are allowed.
* Ability to take oral medication and be willing to adhere to the study intervention.

Exclusion Criteria:

* Pre-treatment tumor biopsy sample not likely to provide adequate tissue sections for biomarker assays.
* Inoperable or metastatic disease.
* Subjects who have received any prior therapy for breast cancer, including radiotherapy, surgery, and cytotoxic and endocrine treatments.
* The subject must not have had hormonal therapy for breast cancer treatment or for breast cancer prevention within 1 year prior to study enrollment. (Note: Synchronous breast, cancer (including bilateral breast cancer) at separate sites is permissible, provided the patient does not receive medical treatments for breast cancer or radiation therapy to the ipsilateral breast during the study intervention period.
* Subjects with plans to undergo neoadjuvant chemotherapy.
* Use of hormonal contraceptives within 6 months of diagnosis.
* Treatment with another investigational drug or other intervention within 28 days before the first administration of letrozole.
* History of allergic reactions/hypersensitivity attributed to compounds of similar chemical or biologic composition to letrozole or any ingredients.
* Uncontrolled current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.