The clinical course of breast cancer patients with brain metastases (BM) as only metastatic site (brain-only metastatic breast cancer (BO-MBC)) has been insufficiently explored.All breast cancer patients with BM treated at our institution between 1990 and 2011 were identified. For each patient, full information on follow-up and administered therapies was mandatory for inclusion. Oestrogen receptor, progesterone receptor and Her2 status were determined according to standard protocols. Statistical analyses including computation of survival probabilities was performed.In total, 222 female patients (26% luminal; 47% Her2; 27% triple negative) with BM of MBC were included in this study. In all, 38/222 (17%) BM patients did not develop extracranial metastases (ECM) during their disease course and were classified as BO-MBC. Brain-only-MBC was not associated with breast cancer subtype or number of BM. The median overall survival of BO-MBC patients was 11 months (range 0-69) and was significantly longer than in patients with BM and ECM (6 months, range 0-104; P=0.007). In all, 7/38 (18%) BO-MBC patients had long-term survival of >3 years after diagnosis of BM and long-term survival was significantly more common in BO-MBC patients as compared with BM patients with ECM (P<0.001).Brain-only metastatic behaviour occurs in around 17% of breast cancer with BM and is not associated with breast cancer subtype. Exploitation of all multimodal treatment options is warranted in BO-MBC patients, as these patients have favourable prognosis and long-term survival is not uncommon.
Breast cancer is the most prevalent malignant disease in women worldwide. Traditionally, surgical tumour resection was the primary step within the treatment algorithm of early stage disease; systemic therapy in order to reduce the rate of systemic recurrences followed. National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-18 found that pre- and postoperative administration of chemotherapy was equally effective. This study therefore established neoadjuvant chemotherapy as a valid treatment option, as the breast conservation rate is increased. Modern neoadjuvant regimens encompassing anthracyclines and taxanes yield pathological complete response (pCR) rates of around 20%, with higher efficacy observed in triple-negative tumours. The antibody trastuzumab is the first targeted agent established in neoadjuvant regimens for the treatment of Her2-positive breast cancer, as it raised pCR rates up to 50%. Novel approaches are aiming to increase the efficacy of neoadjuvant therapy. Inclusion of capecitabine might further increase pCR rates in selected patients, although data are not unanimous throughout the respective clinical trials. In patients harbouring BRCA-1 germline mutations, platinum derivatives are apparently promising. Novel Her2-targeted agents such as lapatinib and pertuzumab are currently under investigation in several clinical trials, while the role of bevacizumab, a monoclonal antibody inhibiting angiogenesis, awaits future clarification.
Background Dose‐dense (DD) adjuvant chemotherapy improves outcomes in early breast cancer (BC). However, there are no phase 3 randomized data to inform on its combination with trastuzumab for patients with human epidermal growth factor receptor 2 (HER2)–positive disease. Methods This was a protocol‐predefined secondary analysis of the randomized phase 3 Pan‐European Tailored Chemotherapy (PANTHER) trial. Women 65 years old or younger with node‐positive or high‐risk, node‐negative BC were randomized 1:1 to either tailored (according to hematologic nadirs) and DD epirubicin and cyclophosphamide followed by docetaxel or standard 5‐fluorouracil, epirubicin, and cyclophosphamide plus docetaxel every 3 weeks. Patients with HER2‐positive disease received 1 year of adjuvant trastuzumab. The primary endpoint was BC relapse–free survival. In addition, HER2‐positive patients and an equal number of HER2‐negative patients matched for age, treatment group, and institution who were enrolled at Swedish sites were asked to participate in a predefined study of cardiac safety and underwent echocardiography or multigated acquisition scanning and electrocardiography at the baseline and at 4 and 6 years of follow‐up. Results There were 342 HER2‐positive patients; 335 received at least 1 dose of trastuzumab, and 29 patients discontinued trastuzumab prematurely. Relapse‐free survival was not statistically significantly in favor of the tailored and DD group (hazard ratio, 0.68; 95% confidence interval, 0.37‐1.27; P = .231). Cardiac outcomes after 4 and 6 years of follow‐up did not differ significantly between HER2‐positive and HER2‐negative patients or between the 2 treatment groups. Conclusions The combination of DD chemotherapy and trastuzumab decreased the relative risk for relapse by 32% in comparison with standard treatment, a statistically nonsignificant difference. Its efficacy and safety merit further evaluation as part of both escalation and de‐escalation strategies.
Abstract Purpose: Denosumab, a fully human monoclonal antibody to RANKL, suppresses bone resorption. This study evaluated the effects of denosumab in i.v. bisphosphonate (IV BP)–naïve patients with breast cancer-related bone metastases. Experimental Design: Eligible women (n = 255), stratified by type of antineoplastic therapy, were randomized to 1 of 5 blinded denosumab cohorts or an open-label IV BP cohort. Denosumab was administered s.c. every 4 weeks (30, 120, or 180 mg) or every 12 weeks (60 or 180 mg) through 21 weeks. Final efficacy results for up to 25 weeks are reported, including percentage change from baseline in urine N-telopeptide corrected for creatinine (uNTx/Cr) and incidence of skeletal-related events (SRE). Safety results are reported through the end of follow-up (up to 57 weeks). Results: At week 13 and 25, the median percent changes in uNTx/creatinine (Cr) among patients with measurable uNTx were −73% and −75% for the pooled denosumab groups and −79% and −71% for the IV BP group. Among patients with ≥1 postbaseline measurement of uNTx at week 25, 52% (109 of 208) of denosumab-treated patients and 46% (19 of 41) of IV BP–treated patients achieved >65% uNTx/Cr reduction. On-study SREs occurred in 12% (26 of 211) of denosumab-treated patients and 16% (7 of 43) of IV BP–treated patients. Overall rates of adverse events were 95% in denosumab and IV BP groups. No denosumab-related serious or fatal adverse events occurred. Conclusions: In IV BP–naïve breast cancer patients with bone metastases, denosumab suppresses bone turnover and seems to reduce SRE risk similarly to IV BPs, with a safety profile consistent with an advanced cancer population receiving systemic therapy.
Abstract Background: In the metastatic and neoadjuvant settings, bevacizumab (BEV) significantly improves progression-free survival and pathologic complete response rates, respectively, when combined with chemotherapy (CT) for breast cancer. In contrast, accumulating phase III data in the adjuvant setting in both colon and breast cancers have not shown a benefit from the addition of 1 year of BEV to standard therapy. Primary efficacy results from the BEATRICE trial in early triple-negative breast cancer (TNBC) showed no significant difference in invasive disease-free survival (IDFS; primary outcome measure) between adjuvant BEV and non-BEV regimens after events in 393 (15%) of the 2591 randomized patients (stratified hazard ratio 0.87 [95% CI 0.72–1.07]) [Cameron et al. Lancet Oncol 2013]. The low number of events at the prespecified primary analysis of BEATRICE, the largest prospective trial in patients with centrally confirmed early TNBC, suggested that the prognosis for patients with TNBC was better than previously thought. This observation, together with data from retrospective series suggesting that most recurrences occur within 3–5 years of TNBC diagnosis [Dent et al. 2007], makes longer follow-up important to fully understand outcomes in this patient population and the natural history of TNBC. We now report extended follow-up data from the prespecified overall survival (OS) analysis of BEATRICE. Methods: Eligible patients in the open-label randomized multinational phase III BEATRICE trial had centrally confirmed triple-negative and/or basal-like operable primary invasive breast cancer (pT1a-pT3). CT (anthracycline and/or taxane based) was selected by the investigator for each patient. After definitive surgery, patients were randomized 1:1 to receive ≥4 cycles of either CT alone or the same CT + 1 year of BEV (5 mg/kg/wk equivalent). Stratification factors were nodal status (0 vs 1-3 vs ≥4 involved nodes), selected CT backbone (anthracycline vs taxane vs both), hormone receptor status (negative vs low), and surgery (breast conserving vs mastectomy). Secondary outcome measures were OS, breast cancer-free interval, disease-free survival (DFS), distant DFS, and safety (NCI CTCAE v3.0). The prespecified final OS analysis will be performed approximately 52 months after randomization of the last patient into the study. Results: The planned clinical cut-off date is June 30, 2014, when the duration of follow-up will be 4.3–6.5 years in those who have not died or been lost to follow-up. OS (with at least 284 events; 11%), updated IDFS with longer follow-up, and long-term safety results will be analyzed and reported. Citation Format: Richard Bell, Julia Brown, Mahesh Parmar, Mark Toi, Thomas Suter, Guenther Steger, Xavier Pivot, John Mackey, Christian Jackisch, Rebecca Dent, Peter Hall, Almut Mecke, Leilani Morales, Louise Provencher, Elzbieta Staroslawska, Roberto Hegg, Laurence Vanlemmens, Andreas Kirsch, Andreas Schneeweiss, Norikazu Masuda, Friedrich Overkamp, David Cameron. Final efficacy results of the randomized phase III BEATRICE trial evaluating adjuvant bevacizumab-containing therapy in triple-negative early breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr PD2-2.
