Denise A. Yardley, MD: Taxane Resistance

Dr. Yardley says that definition of taxane resistance in this patient is a difficult one to establish; however, the general threshold is at <12 months&rsquo; relapse from initial exposure. The ability to identify molecular markers would be of benefit and, to date, has focused on some of the following: the tubulin-binding site mutations, the ATP-binding cassette transporters, inhibition of apoptotic signaling, and even the estrogen receptor. Emergence of molecular resistance does decrease the efficacy to other chemotherapies by cross-resistance. In a real-world setting, it is difficult to define resistance, as it could simply mean a patient has been exposed to a drug in the past, and has progressed. Resistance is likely on a continuum with the strictest definition, encompassing a patient progressing right through an agent or combination of agents without deriving any meaningful response. Whether this patient has partial taxane resistance or bad biology or both, a taxane rechallenge remains an option, particularly with a different agent and schedule and with a combination chemotherapy strategy.

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.