Metastatic breast cancer subtypes and central nervous system metastases

e11581 Background: The relapse pattern, survival and response to therapy are known to be different between breast cancer (BC) subtypes defined by combining hormone-receptor (HR) and HER2 status. Our aim was to study incidence and predictors of central nervous system metastases (CNS-M) and the outcome after CNS-M according to tumor subtype. Methods: 488 patients (pts) treated with at least one line of chemotherapy for metastatic BC were retrospectively evaluated. According to the combination of HR and HER2 status, tumors were grouped in: Luminal (Lum): HR+/HER2-, Luminal/HER2+ (Lum/HER2+): HR+/HER2+, pure HER2 positive (pHER2+): HR-/HER2+, and triple negative (TN): HR-/HER2-. All HER2+ patients received treatment with Lapatinib or Trastuzumab in addition to chemotherapy for metastatic disease. Median follow up was 34 months. Results: 133 pts (27%) developed CNS-M, with a median time to CNS progression of 43 months. The rate of CNS-M by subtype was: Lum 18%, Lum/HER2+ 37%, pHER2+ 49%, TN 25% (p <0.001). Multivariate analysis confirmed that, compared with Lum tumors, Lum/HER2+ ( HR 2.556, p<0.001), pHER2+ (HR 4.444, p<0.001) and TN (2.249, p=0.011) subtypes were at higher risk of CNS-M. Median overall survival (OS) CNS-M was 8.8 months in the whole series (IC 95% 6.6-11.0). Median OS in months by subtype was: Lum 9, Lum/HER2+ 18, pHER2+ 7, TN 7 (p<0.001). Multivariate analysis revealed that belonging to the Lum/HER2+ subtype (HR 0.528 compared with the Lum subtype, p<0.001) and having isolated CNS (HR 0.398, compared with CNS-M plus systemic progression, p<0.001) predicted significantly reduced risk of death. Conclusions: Among pts with a known increased risk of brain metastases, the Lum/HER2+ subtype appears associated with the longest OS after CNS-M, probably due to different biology and better extracranial disease control by chemotherapy, hormonal therapy and target agents. These results suggest that these patients may benefit from a more aggressive treatment of CNS-M and, possibly, from the screening for asymptomatic CNS lesions

Underuse of Anthracyclines in Women with HER-2+ Advanced Breast Cancer

This article examines how discouraging the use of anthracyclines in combination with trastuzumab in patients with human epidermal growth factor receptor 2 positive metastatic breast cancer because of fears of cardiotoxicity has influenced the use of these agents in this patient setting

Vinorelbine-based salvage therapy in HER2-positive metastatic breast cancer patients progressing during trastuzumab-containing regimens: a retrospective study

<p>Abstract</p> <p>Background</p> <p>The vinka-alkaloyd vinorelbine is a potentially valuable treatment in patients with HER2-positive, trastuzumab-resistant advanced breast cancer. We sought to document the clinical activity of vinorelbine-based salvage treatments in this clinical setting.</p> <p>Methods</p> <p>We analyzed a cohort of 424 consecutive women receiving trastuzumab-based therapy for HER2-positive advanced breast cancer. Of these, 299 were identified as progressing during the initial trastuzumab-based treatment, and 77 received vinorelbine-based therapy as first salvage treatment. Central review of pathological specimens revealed that 70 patients had HER2-amplification detected by FISH. For these patients we determined overall response rate (ORR = complete-CR + partial-PR) and clinical benefit (CB = CR+PR+ Stable disease lasting at least 6 months), time to progression (TTP) and overall survival (OS) from the initiation of vinorelbine-based salvage therapy.</p> <p>Results</p> <p>In 60 patients who were evaluable for tumor response, ORR and CB rates were 28% (95% C.I. 18%-41%) and 50% (95% C.I. 38%-62%), respectively. Median follow-up from the initiation of salvage therapy was 15 months (range 1–63 months). Median TTP and OS were 7.1 months (95% C.I. 6.6–7.7 months) and 21 months (95% C.I. 14.3–27.7 months), respectively. No differences in clinical outcomes were observed according to whether vinorelbine was administered as a single agent or in combination with other cytostatics, or whether trastuzumab was stopped or continued beyond disease progression.</p> <p>Conclusion</p> <p>our findings suggests that vinorelbine-based combinations are active and should be further evaluated in studies conducted in trastuzumab-resistant patients, including those evaluating newer HER2-targeting agents.</p

Trastuzumab Beyond Progression in Retrospective Analyses: An Issue of Equal Opportunities

Results of the Hermine study of trastuzumab beyond progression in breast cancer patients, published by Extra and colleagues in The Oncologist, are re-examined and an alternative explanation for the dismal postprogression survival time of patients stopping therapy is presented

Trastuzumab with either docetaxel or vinorelbine as first-line treatment for patients with HER2-positive advanced breast cancer: a retrospective comparison

Abstract Background Combinations of trastuzumab with either docetaxel or vinorelbine are considered valuable treatment options for HER2-positive metastatic breast cancer patients. We performed a retrospective comparison of the clinical outcomes associated with either one of these combinations. Methods From a multi-institutional database we retrieved 179 patients treated with either docetaxel or vinorelbine plus trastuzumab as first-line therapy for HER2-positive advanced breast cancer. Results Docetaxel-trastuzumab was superior to vinorelbine-trastuzumab in terms of response rate (RR: 77 vs 57%, p = 0.01) and median overall survival (OS: 35 vs 23 months, p = 0.04), but not in median time to progression (TTP: 12 vs 10 months, p = 0.53). At multivariate analysis, type of treatment was not associated with TTP but was an independent predictor of OS, with a significant reduction in the risk of death in favor of docetaxel-trastuzumab (HR 0.474, 95% IC 0,303-0.742, p Conclusion Docetaxel or vinorelbine, when combined with trastuzumab, provide excellent rates of tumor control in patients with previously untreated HER2-positive advanced breast cancer. Docetaxel may offer some advantage in terms of response rate and resulted in a significantly prolonged overall survival, which, because of the retrospective design of our study, deserves further investigation in prospective trials.</p

Underuse of Anthracyclines in Women with HER-2 ϩ Advanced Breast Cancer Oncologist ® Breast Cancer

ABSTRACT Anthracyclines are among the most active drugs in breast cancer. Because of excessive cardiotoxicity, their use in combination with trastuzumab has been discouraged in patients with human epidermal growth factor receptor (HER)-2 ؉ metastatic breast cancer. We sought to describe how this treatment paradigm influenced the use of anthracyclines in this patient setting. We analyzed a multi-institutional database containing the treatment history of 450 patients who received at least one trastuzumab-based regimen for HER-2 ؉ metastatic breast cancer. Patients were considered eligible for anthracyclines for metastatic disease if they were never exposed (NE) or had been previously exposed (PE) to an anthracycline in the neoadjuvant or adjuvant setting and had relapsed after 12 months from the last dose. We then assessed the use of anthracycline-based therapy after failure with the first trastuzumab-based regimen in eligible patients. Three-hundred twenty-one patients were considered eligible for anthracyclines. In total, 190 eligible patients developing disease progression during the initial trastuzumab-based therapy were analyzed. An anthracycline was administered as first salvage treatment in 14 NE and two PE patients. Another 15 NE and nine PE patients received an anthracycline as a further line of therapy. Of 119 eligible patients who died from breast cancer, only 30 received an anthracycline for metastatic disease. In conclusion, despite the fact that two thirds of the patients receiving trastuzumab-based therapy for HER-2 metastatic breast cancer are eligible for an