Board Review

A 34-year-old woman is evaluated for a 4-week history of tenderness in her left lower breast. Her paternal grandmother died of ovarian cancer at age 54 years. There is no family history of breast cancer. She has a 2-cm palpable left lower outer breast mass on exam. The remainder of the examination is unremarkable.

Results of complete blood count and serum chemistry panel are normal. A mammogram shows increased density and calcifications at the site of the palpable mass. Ultrasound examination reveals a 1.9-cm hypoechoic mass. Ultrasound-guided needle biopsy specimens show a high-grade invasive ductal carcinoma, estrogen receptor–negative, progesterone receptor–negative, and negative for HER2 amplification.

Which of the following is the most appropriate initial management?

A) Bilateral mastectomy

B) BRCA1/2 testing

C) Left mastectomy

D) Lumpectomy with sentinel lymph node biopsy

Answer: B - BRCA1/2 testing

Objective: Determine indications for BRCA1/2 testing in a woman with newly diagnosed breast cancer.

Key Point

Offering BRCA1/2 testing prior to surgery is recommended for patients diagnosed with breast cancer before age 45 years, patients with breast cancer at any age and a family history of breast and/or ovarian cancer, and patients with triple-negative breast cancers diagnosed before age 60 years.

This patient should be offered BRCA1/2 testing before surgical treatment is recommended. Offering BRCA1/2 testing prior to surgery is recommended for patients younger than 45 years with either newly diagnosed breast cancer or a family history of breast or ovarian cancer. BRCA1/2 testing is also recommended for patients with breast cancer diagnosed at any age if one or more first-, second- or third-degree relatives have been diagnosed with ovarian cancer and is recommended for women with “triple negative breast cancer” (estrogen receptor–negative, progesterone receptor–negative, and negative for HER2 amplification) diagnosed before age 60 years. Because this patient was diagnosed with breast cancer at age 34 years and has a family history of ovarian cancer in a paternal grandmother, she has an 18% risk of having a BRCA1/2 mutation. Offering BRCA1/2 testing prior to breast surgery is therefore recommended, particularly if the result will influence the patient's choice of surgery. If she tests positive for a BRCA1 or BRCA2 mutation, bilateral mastectomy should be considered because of the high risk for subsequent contralateral and ipsilateral breast cancers. The lifetime risk of contralateral breast cancer in women with breast cancer and a BRCA1/2 mutation is 40% to 60%. The risk is highest in women younger than 40 years of age at diagnosis. In the United States, 50% to 70% of women with breast cancer who have a BRCA1/2 mutation elect bilateral mastectomy, and studies suggest a survival benefit of prophylactic contralateral mastectomy in this situation.

If the patient were to test negative for a BRCA1/2 mutation, bilateral mastectomy would not be recommended.

Left mastectomy is not usually required for a 2-cm breast cancer amenable to breast-conserving treatment, although it is an option if patients want to avoid radiation or have contraindications to radiation therapy. In addition, left mastectomy would not decrease the high risk of contralateral breast cancer for patients with a BRCA1/2 mutation.

Lumpectomy with sentinel lymph node biopsy, followed by breast radiation therapy, is a reasonable option in patients with tumors measuring less than 5 cm that can be resected with clear margins. Survival following breast conservation therapy is equal to mastectomy in patients without BRCA1/2 mutations.

Malone KE, Begg CB, Haile RW, et al. Population-based study of the risk of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2. J Clin Oncol. 2010 May 10;28(14):2404-10. Link Out