Denise A. Yardley, MD: Triple-Negative Phenotype's Influence on Treatment

This aggressive disease often is accompanied by a lower threshold of parameters to trigger treatment recommendations in early-stage disease, based on the inability to administer antiestrogen or HER2-targeted therapies. It is extremely important to recognize that not all early-stage TNBC will relapse. However, the biology of a small node-negative, triple-negative early-stage breast cancer remains aggressive and is a factor to consider when making treatment recommendations for adjuvant chemotherapy, where the benefit of taxanes in TNBC has been recognized.

In an important subset analysis of the CALGB 9344/INT0148 trials, the addition of paclitaxel to AC chemotherapy was associated with improved disease-free survival in the HER2- and in the hormone receptor-negative subgroup, providing additional support that TNBC derives substantial benefit from the addition of paclitaxel in the adjuvant setting and reinforcing the conclusion that taxanes are important in TNBC. The benefit of the taxanes in the triple-negative phenotype has also been highlighted in additional trials even in the neoadjuvant setting, where a pre-op study adding taxanes to FAC chemotherapy resulted in a higher partial complete response rate in the basal TNBC subgroup. While newly diagnosed patients with metastatic breast cancer treated with taxanes lived as long as those treated with anthracyclines, combinations with taxanes provided better response rates and progression-free survival than those based on anthracyclines.

CASE 2: Triple-Negative Breast Cancer

Arlene C. is a 40-year-old premenopausal white woman from Cleveland who works as a pharmaceutical sales representative.

In November 2012, she was referred by her PCP for imaging and further evaluation after her initial mammography returned an abnormal result.

Mammography showed a 2.0-cm tumor

Core biopsy tested positive for IDC in left-lower outer quadrant (negative for ER and PgR; HER2 IHC 2+, but FISH-negative)

Patient’s family history was unremarkable for breast cancer; she declined genetic testing

Patient received breast-conserving surgery; sentinel lymph node evaluation was negative

Tumor classified as Stage 1A (T1bN0M0)

Patient received adjuvant TC chemotherapy (docetaxel 75 mg/m2 IV day 1, cyclophosphamide 600 mg/m2 IV day 1 cycled every 21 days for 4 cycles) with pegfilgrastim support, with subsequent adjuvant radiotherapy

In December 2013, patient returns to PCP complaining of intermittent cough and dyspnea; she is referred back to her oncologist for further workup.

PET scan showed evidence of local recurrence in the left breast and multiple lung nodules; bone scan showed a rib lesion

Having progressed within 12 months of her TC regimen, patient is considered partially taxane resistant

Biopsy of breast and lung nodule was consistent with the primary tumor’s phenotype

Gemcitabine/carboplatin chemotherapy was administered for metastatic disease (gemcitabine 1000 mg/m2 days 1 and 8, carboplatin AUC 2 IV, days 1 and 8, cycled every 21 days)

Following the 6th cycle, patient is unable to work with increasing fatigue, intermittent rib pain, and worsening dyspnea.