Patient case: 56-year-old female with breast cancer; genetic feature: ERBB2

Clinical trial: Neoadjuvant Study of Two Platinum Regimens in Triple Negative Breast Cancer

Summary: Evaluate if the two carboplatin containing chemotherapy regimens will reduce the growth of breast cancer cells in women with Stage I, II, or III triple negative breast cancer.

Detailed description: Sporadic and germline BRCA mutation associated triple-negative breast cancer share several pathological and molecular similarities which have led to the exploration of DNA damaging agents like platinum compounds in patients with triple-negative breast cancer. Recent studies demonstrate that addition of neoadjuvant carboplatin to doxorubicin/cyclophosphamide/taxane-based chemotherapy improves pathological complete response in patients with stage I-III triple-negative breast cancer but also increase toxicity.
  A recent study reported encouraging pathological complete response rates with a non-anthracycline carboplatin plus docetaxel neoadjuvant chemotherapy regimen in a cohort of 49 triple negative breast cancer patients. This chemotherapy regimen of carboplatin plus docetaxel yielded an overall pathological complete response rate of 65% in unselected triple-negative breast cancer with pathological complete response rates of 61% in sporadic and 77% in germline BRCA-associated triple-negative breast cancer. The chemotherapy regimen of carboplatin/docetaxel is well tolerated and should be studied further and compared with regimens that add carboplatin to the standard anthracycline/taxane containing regimens.
  This is the basis for the proposed randomized neoadjuvant phase II study to further estimate and compare pathological complete response rates of carboplatin plus docetaxel x 6 cycles to carboplatin plus paclitaxel x 4 cycles followed by doxorubicin plus cyclophosphamide x 4 cycles in stage I-III triple negative-breast cancer.

Eligibility: Inclusion Criteria:
  -  Patients with newly diagnosed stage I (T>1cm), II or III triple negative breast cancer who have not had definitive breast surgery or received systemic chemotherapy
  -  The invasive tumor must be hormone receptor-poor, defined as both estrogen receptor and progesterone receptor staining present in ≤ 10% of invasive cancer cells by Immunohistochemistry.
  -  HER- 2 negativity will be based on the current ASCO-CAP guidelines for HER testing
  -  No prior chemotherapy, endocrine therapy or radiation therapy with therapeutic intent for this cancer
  -  Female subjects age 18 - 70 years
  -  ECOG Performance Status of 0-1
  -  Adequate organ and marrow function as defined below:
  -  Leukocytes ≥ 3,000/uL
  -  Absolute neutrophil count ≥ 1500/uL
  -  Platelets ≥ 100,000/uL
  -  Total bilirubin ≤ 1.5mg/dL
  -  AST(SGOT)/ALT(SPGT) ≤ 2 x institutional upper limit of normal
  -  Creatinine ≤ 1.5mg/dl and/or Creatinine Clearance ≥ 60mL/min
  -  Serum albumin ≥ 3.0 g/dL
  -  Women of child-bearing potential must agree to use adequate contraception
  -  Pretreatment lab values must be performed within 14 days of treatment initiation, and other baseline studies performed within 30 days prior to registration
  -  Subjects should have LVEF ≥ 50% by echocardiogram or MUGA scan performed within 4 weeks prior to treatment initiation
  -  Subjects should have breast and axillary imaging with breast MRI or breast and axillary ultrasound within 4 weeks prior to treatment initiation
  -  Subjects with clinically/radiologically abnormal axillary lymph nodes should have pathological confirmation of disease with image guided biopsy/fine needle aspiration.
  -  Subjects must be already enrolled in P.R.O.G.E.C.T observational registry
  -  Staging to rule out metastatic disease is recommended for subjects with clinical stage III disease
  -  Subjects with bilateral disease are eligible if they meet other eligibility criteria.
  -  Neuropathy: No baseline neuropathy grade > 2
  Exclusion Criteria:
  -  Current or anticipated use of other investigational agents
  -  Subject has received chemotherapy, radiotherapy or surgery for the treatment of breast cancer
  -  Subject with metastatic disease
  -  History of allergic reactions to compounds of similar chemical or biologic composition to carboplatin, docetaxel, doxorubicin, cyclophosphamide, paclitaxel, or other agents used in the study
  -  Subjects with inflammatory breast cancer
  -  Uncontrolled intercurrent illness including, but not limited to ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
  -  Subject is pregnant or nursing
  -  Subjects with concomitant or previous malignancies within the last 5 years. Exceptions include: adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and ductal carcinoma in situ (DCIS).
  -  Ejection Fraction <50% on ECHO or MUGA
  -  Cardiac function: Subjects with congestive heart failure, myocardial infarction, unstable angina pectoris, an arterial thrombotic event, stroke or transient ischemia attack within the past 12 months, uncontrolled hypertension (Systolic BP>160 or Diastolic BP>90), uncontrolled or symptomatic arrhythmia, or grade ≥ 2 peripheral vascular disease

Relevance to patient case: not relevant