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Breast Cancer Case Studies

Denise A. Yardley, MD: Taxane Resistance

Denise A. Yardley, MD
Published Online:Jun 18, 2015
Arlene C. is a 40-year-old premenopausal white woman from Cleveland who works as a pharmaceutical sales representative.

Triple-Negative Breast Cancer: Case 2

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’ 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.
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