Grand Rounds

Hereditary Breast and Ovarian Cancer Syndrome

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ABSTRACT

Case Study

A.G. is a 56-year-old Caucasian female with metastatic breast cancer who was originally diagnosed with breast cancer at age 41, in 1995, when she presented to her primary care physician with a right breast mass. This was the same year that BRCA1 and BRCA2 mutations were being discovered. A biopsy was done, revealing her mass to be a 2.8-cm infiltrating ductal carcinoma that was grade 3 ER/PR positive. She was staged as T2NxMx. She underwent a right modified radical mastectomy with reconstruction with a transverse rectus abdominis myocutaneous (TRAM) flap. Pathology revealed 0 out of 13 nodes to be positive.

A.G. received adjuvant therapy with 4 cycles of doxorubicin/cyclophosphamide followed by 5 years of tamoxifen. There was no evidence of disease for 13 years, until 2008, when A.G. developed right upper arm swelling; venous Doppler revealed an occlusive thrombus in the right axillary vein. A chest CT scan showed osseous metastatic disease involving the sternum and anterior right first rib with an extraosseous soft-tissue mass. There was also a small right pleural effusion, suspicious mediastinal lymph nodes, and multiple pulmonary nodules.

A bone scan confirmed multiple skeletal metastases involving the left posterior skull, right first rib, sternum, left posterior iliac bone, and left femoral head. One of the nodules was biopsied, revealing metastatic carcinoma compatible with breast primary. A.G. was started on zoledronic acid (Zometa) and letrozole in April 2008. In July 2008, a CT scan of the chest showed interval resolution of the thoracic adenopathy, near resolution of the bilateral pulmonary nodules, and mixed lytic and blastic lesions involving the bones. Fulvestrant (Faslodex) was then added to the treatment plan. In January 2009, A.G. was switched to tamoxifen and fulvestrant was discontinued.

In June 2009, PET scan revealed an increase in the size of the parasternal mass along with increased density in the mediastinum. Estradiol was added outside of a clinical trial. Follow-up PET/CT in September 2009 showed significant progression, and A.G. was switched to exemestane. She had spent a total of 4 months on estradiol. One may question the use of estradiol in hormone receptor–positive breast cancer. This was actually examined as practice between 2004 and 2008 in an effort to resensitize to estrogen deprivation in postmenopausal women in aromatase inhibitor–resistant breast cancer (National Cancer Institute, 2010). In this case, the problem is that A.G. was not given any aromatase inhibitors at this point; this practice could very well have contributed to the progression of her disease.

By November 2009, A.G.’s CEA and CA 15-3 levels started to rise, and she was found to have right supraclavicular, axillary, subclavian, mediastinal, parasternal, and pleural-based metastatic disease. Exemestane was stopped and A.G. was started on capecitabine (Xeloda). In February 2010, she received radiation to the T10 and L1 vertebrae for her bone metastases.

In March 2010, PET/CT revealed innumerable hypermetabolic soft-tissue masses in the lymph nodes, lung nodules, and bones. Five radiation treatments were delivered to the sternum and right chest wall in July 2010. By the end of July, A.G. developed a large pleural effusion and underwent an ultrasound-guided thoracentesis, withdrawing 1.5 L of pleural fluid that was positive for metastatic adenocarcinoma. Capecitabine was stopped at this time due to progression, and she was told by her oncologist that nothing more could be done.

A.G. self-referred to another oncologist in July 2010. Family history revealed that her mother had been diagnosed with breast cancer at age 48, and that her two sisters were diagnosed with breast cancer at ages 45 and 47 and found to be BRCA2-positive with deleterious mutations noted at 6855ins TA. One sister had the full BRACAnalysis in February 2010 and the other sister was tested for specific mutation in April 2010. Although their mother was the first to be diagnosed with breast cancer, it was more than 20 years ago; she did not choose to have any type of genetic testing done. A.G. reported that she had been tested with the full BRCA panel in February 2009 and had been found to be negative. (See the accompanying text for more information about A.G.’s case.)

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