Neoadjuvant doxorubicin/cyclophosphamide followed by ixabepilone or paclitaxel in early stage breast cancer and evaluation of ßIII-tubulin expression as a predictive marker.

BACKGROUND: This randomized phase II trial was designed to compare the rate of pathologic complete response (pCR) induced by neoadjuvant cyclophosphamide plus doxorubicin (AC) followed by ixabepilone or paclitaxel in women with early stage breast cancer (BC). Expression of ßIII-tubulin as a predictive marker was also evaluated. PATIENTS AND METHODS: Women with untreated, histologically confirmed primary invasive breast adenocarcinoma received four cycles of AC followed by 1:1 randomization to either ixabepilone 40 mg/m2 (3-hour infusion) every 3 weeks for four cycles (n = 148) or weekly paclitaxel 80 mg/m2 (1-hour infusion) for 12 weeks (n = 147). All patients underwent a core needle biopsy of the primary cancer for molecular marker analysis prior to chemotherapy. ßIII-Tubulin expression was assessed using immunohistochemistry. RESULTS: There was no significant difference in the rate of pCR in the ixabepilone treatment arm (24.3%; 90% confidence interval [CI], 18.6-30.8) and the paclitaxel treatment arm (25.2%; 90% CI, 19.4-31.7). ßIII-Tubulin-positive patients obtained higher pCR rates compared with ßIII-tubulin-negative patients in both treatment arms; however, ßIII-tubulin expression was not significantly associated with a differential response to ixabepilone or paclitaxel. The safety profiles of both regimens were generally similar, although neutropenia occurred more frequently in the ixabepilone arm (grade 3/4: 41.3% vs. 8.4%). The most common nonhematologic toxicity was peripheral neuropathy. CONCLUSIONS: Neoadjuvant treatment of early stage BC with AC followed by ixabepilone every 3 weeks or weekly paclitaxel was well tolerated with no significant difference in efficacy. Higher response rates were observed among ßIII-tubulin-positive patients.

A Comparison of Clinical Features, Pathology and Outcomes in Various Subtypes of Breast Cancer in Indian Women.

BACKGROUND: Breast cancer is often classified into subtypes using immunohistochemical markers. These subtypes have distinct biological behaviour. This study was conducted with the aim of estimating the distribution of various subtypes of breast cancer in Indian population based on immunohistochemistry markers and to determine the clinical features, pathology and outcomes of these subtypes of breast cancer. MATERIALS AND METHODS: A retrospective study was undertaken and all patients of breast cancer over a 5 year period were included. These patients were divided into 4 subgroups depending on the presence or absence of immunohistochemical markers: i) Luminal A (ER/PR+, Her 2 neu-); ii) Luminal B (ER/PR+, Her 2 neu+); iii) Her 2 enriched (ER-/PR-, Her 2 neu+) and; iv) Triple negative (ER-, PR-, Her2 neu-). Clinical and pathological features and survival were compared between patients in the 4 subgroups. RESULTS: Luminal A subgroup had majority of patients (43.8%). Patients in Luminal B, Her 2 enriched, and Triple negative subgroups were 14.8%, 16.1% and 25.3%. Median follow-up of patients was for 34 months. Luminal A subgroup patients were more likely to be postmenopausal and have smaller and lower grade (I/II) tumours with better survival (OS-91.06%). Patients in the Triple negative subgroup were more likely to be premenopausal (p-value 0.036, odds ratio 0.611, CI 0.394-0.949), have larger and higher grade (III) tumours with worse overall survival (OS-88.46%, odds ratio 1.32, 95%CI 0.602-2.39). Her 2 enriched group patients had bad prognostic features like larger size of tumour and higher grade of tumour and worst survival among all the subgroups (OS-85.07%, odds ratio 1.78, 95% CI 0.767-4.163). However, these outcomes were not statistically significant for the subgroups. CONCLUSION: A retrospective study was undertaken of breast cancer patients in India, according to subtypes based on immunohistochemistry. Luminal A had prognostic features and survival which was better as compared to other subgroups (Luminal B, Her 2 enriched and Triple negative). Incidence of patients with Triple negative breast cancer was higher in the premenopausal period. Patients with Her 2 enriched breast cancer had the worst survival among all the subgroups.

Gemcitabine plus Paclitaxel versus Paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment.

PURPOSE: The objective of this phase III global study was to compare the efficacy of gemcitabine plus paclitaxel (GT) versus paclitaxel in patients with advanced breast cancer. It was designed as a pivotal study for the approval of G for a breast cancer treatment indication. PATIENTS AND METHODS: Patients who relapsed after adjuvant anthracyclines were randomly assigned to gemcitabine,1,250 mg/m(2) days 1 and 8 plus paclitaxel, 175 mg/m(2) on day 1; or, to paclitaxel at same dose on day 1 (both arms administered every 21 days, unblinded). The primary end point was overall survival (OS) and secondary end points were time to progression (TTP), response rate (RR), progression-free survival, response duration, and toxicity. This final OS analysis was planned at 380 deaths. RESULTS: A total of 266 patients were randomly assigned to GT and 263 to paclitaxel. Median survival on GT was 18.6 months versus 15.8 months on paclitaxel (log-rank P = . 0489), with an adjusted Cox hazard ratio of 0.78 (95% CI, 0.64 to 0.96; P = .0187). The TTP was longer (6.14 v 3.98 months; log-rank P = .0002) and the RR was better (41.4% v 26.2%; P = .0002) on GT. There was more grade 3 to 4 neutropenia on GT and grade 2 to 4 fatigue and neuropathy were slightly more prevalent on GT. CONCLUSION: This phase III study documents a role for gemcitabine in advanced breast cancer after anthracycline-based adjuvant therapy. The results establish GT as a reasonable choice for women who require cytoreduction with manageable toxicities and validate ongoing testing of GT in the adjuvant setting.