Treatment Strategies for Triple-Negative Breast Cancer

Reshma L. Mahtani, DO:Patients who develop recurrence of triple-negative breast cancer are somewhat limited in their options for further treatment based on the fact that they don’t have hormonal therapy as an option and they don’t have HER2-directed therapies as an option. Although we’re eagerly awaiting more data beyond a press release from the IMpassion study that looked at the use of a checkpoint inhibitor in the first line in combination with chemotherapy, we did get a hint that it is a positive study in terms of the primary endpoint of progression-free survival. We don’t have currently an approval in that setting. We’re also waiting for additional treatments that are on the horizon, such as IMMU-132, or sacituzumab govitecan. At the present time, we don’t have any targeted therapy for these patients and chemotherapy is the only option for them.

Fortunately, chemotherapy responses tend to occur at a high rate. But unfortunately, those responses tend to be short-lived. And so, in the academic environment where access to clinical trials is present, these are patients who we prioritize to put on studies. It’s an area of high unmet need. In general, I would say that patients with triple-negative breast cancer don’t go through as many lines of therapy, be it in the community or in the academic setting, mainly because of the fact that they have aggressive disease that tends to have short-lived responses.

When patients recur after an anthracycline and a taxane, chemotherapy at present is the only treatment option for them. We take into account factors such as the burden of disease, how symptomatic the patient is, what toxicities they have from prior therapy, and their goals of therapy. We take all of that into account. Ultimately, we want to get these patients on clinical trials, as I mentioned, because we really are very interested in looking at novel approaches for these patients in an area of high unmet need.

In terms of the treatment that was given, gemcitabine and carboplatin in the first-line setting, we tend to reserve combination chemotherapy for patients who are quite symptomatic, as this patient was. She had a cough and abdominal pain, and we know that these are drugs she hasn’t been exposed to in the adjuvant setting. A combination therapy may be appropriate for her. In addition, we know that platinum drugs may be a particularly important treatment option for patients with triple-negative disease, perhaps even more important for those who areBRCAmutation carriers. But even in this case, I would say it is a very reasonable option in the first-line setting outside the context of the clinical trial.

We were very fortunate to have the approval of a PARP inhibitor, an oral PARP inhibitor, for our patients with a germlineBRCAmutation who have metastatic breast cancer. This approval was on the basis of the OlympiAD trial that was presented last year at ASCO [the American Society of Clinical Oncology meeting]. In this study, women who had a germlineBRCAmutation, metastatic disease, and no more than 2 prior lines of chemotherapy in the metastatic setting were randomized 2-to-1 to chemotherapy of physician’s choice or olaparib. In terms of efficacy, we saw about a 3-month improvement over chemotherapy with the use of the PARP inhibitor. This treatment was generally well tolerated, and I would say better tolerated than chemotherapy with less discontinuation due to side effects. And in general, olaparib was also associated with a higher response rate.

This led to the approval of olaparib for germlineBRCAmutation carriers and represents an important improvement, I would say, in treatment options. Unfortunately, these drugs are only available for patients withBRCAmutations and, as we know, all triple-negative breast cancer patients don’t harbor aBRCAgene mutation. But for those who do, this is an important treatment that’s now available for them. I would say we should increase awareness about the need to assess family history appropriately and consider testing patients who we may not have considered testing in the past, now that we do have a targeted therapy available to them.

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