Approaching a Case of Triple-Negative Breast Cancer

Reshma L. Mahtani, DO:This is a case of a 55-year-old postmenopausal African American woman. She’s the mother of 2 teenage children, and she palpated a lump in her right breast approximately 2 years ago. At that time, she had imaging that suggested the presence of multifocal disease with the largest tumor by imaging being about 2.5 cm. The imaging also revealed the presence of suspicious axillary lymph nodes, and both the breast mass and the lymph nodes were biopsied and proven to represent invasive ductal cancer: ER and PR-negative, and HER2-negative as well. So, it was a triple-negative tumor.

She wasBRCAtested due to the fact that she had a triple-negative tumor and given her age, butBRCAtesting did not reveal the presence of a gene mutation. Distant disease was not confirmed on imaging and therefore, she was treated with curative intent and actually went through a mastectomy and a lymph node dissection up front. The largest tumor was 2.5 cm, with 2 out of 20 positive axillary lymph nodes. At that point, she was treated with adjuvant chemotherapy, doxorubicin and cyclophosphamide followed by a taxane, and completed that therapy. She tolerated it reasonably well, but did have some issues with nausea, vomiting, and diarrhea. She had a bit of a tough time.

Then on routine follow-up at 18 months, she presented with a cough and abdominal pain. This led to imaging, which unfortunately confirmed the presence of multiple lesions in the lung and liver, which were again biopsied and found to represent triple-negative metastatic breast cancer. In the first-line setting, she was offered combination chemotherapy with gemcitabine and carboplatin, and follow-up imaging at 3 months did show stabilization of disease.

Seven months after starting gemcitabine and carboplatin, she did have progression on imaging with a lung lesion increasing in size to about 3.5 cm. At this point a discussion occurred, and it was decided to treat the patient with capecitabine. She responded to capecitabine for several months but ultimately developed progressive disease and was treated with eribulin.

My initial impressions of this case include the fact that we’re worried about this patient. She has an aggressive tumor. She has a grade 3 tumor. It’s triple negative, and she has lymph node involvement. These are all signs of generally poor prognosis. We know that triple-negative breast cancer accounts for approximately 15% to 20% of all breast cancers and disproportionally affects younger women, women of African American ancestry, and women who have theBRCAgene mutation.

Due to the worse prognosis of this subtype of breast cancer and our increasing understanding of the heterogenous nature of the disease, there has been a general trend or shift in the treatment of these tumors toward more neoadjuvant therapy. We know that neoadjuvant treatment results in a window of opportunity to assess response to treatment, and the achievement of a pathologic complete response is a surrogate for event-free survival. We know that patients who don’t respond well and have residual disease are at higher risk of recurrence, and they are currently the subject of many clinical trials looking at giving additional therapy such as genomically-directed therapy, checkpoint inhibitors, or vaccine studies. Now we also have data for the use of capecitabine in the post—neoadjuvant setting. In my practice, I think this patient would have gotten neoadjuvant therapy for the reasons I discussed.

Transcript edited for clarity.

A 55-year-old Woman With Advanced TNBC

June 2015

• Patient History
  • A postmenopausal 55-year-old African American woman who was first diagnosed with breast cancer 2 years ago after discovering a lump in her right breast
  • SH: active with 2 teenaged children
  • Imaging revealed the likelihood of a multifocal lesion (2.5 cm.) in the right breast and right axillary lymph node involvement
• Pathology findings from ultrasound-guided core needle biopsy:
  • Histologic grade 3 invasive ductal carcinoma
  • Hormone receptor status: ER(-), PR(-)
  • HER2(-) IHC, 0
• BRCA1/2testing, negative
• She underwent mastectomy followed by immediate reconstruction; 2 of 20 nodes positive
  • Surgical staging T2pN1M0
• Following surgery, she received adjuvant doxorubicin/cyclophosphamide followed by paclitaxel (12 weeks); pt. had difficulty completing CT due to significant diarrhea and CINV

October 2017

• Routine follow up at 18 months:
  • Patient reported having worsening cough and abdominal pain
  • Imaging revealed 3 lesions in her right lung (<2 cm) and several liver lesions
  • Biopsy confirmed metastatic TNBC
• She was started on treatment with gemcitabine/carboplatin; she required dose reduction for neutropenia; imaging at 3 months showed stable disease

May 2018

• Seven months after starting gemcitabine/carboplatin, imaging showed progression in a single right lung nodule (now 3.2 cm)
• After discussion of her therapy choices, the patient opted for treatment with capecitabine

August 2018

• Imaging at 3 months showed 4 new liver lesions
• She started treatment with eribulin 1.4 mg/m²IV on days 1 and 8 of each 21-day cycle
  • Two weeks after her first dose, she developed grade 3 neutropenia without fever