Male Breast Cancer in Australia.

AIMS: Male breast cancer is rare and treatment recommendations are based on female breast cancer guidelines. We analyzed an Australian dataset of patients with early breast cancer (including ductal carcinoma in situ, DCIS) for demographic, pathological and treatment information. The primary objective was to compare treatment delivery for males versus females. METHODS: Australian data from the BreastSurgANZ Quality Audit (BQA) from 1 October 2006 and 30 September 2016 were analyzed. Demographic and pathological information was obtained and compared between males and females. Treatment recommendations were compared to BreastSurgANZ Key Performance Indicators (KPIs) and National Comprehensive Cancer Network (NCCN) guidelines to assess for adherence to national and international guidelines, respectively. RESULTS: A total of 99,768 breast cancer episodes were analyzed, comprising 585 males (544 invasive; 41 DCIS) and 99 183 (99.4%) females (85 596 invasive; 13 525 DCIS; 62 unknown). Compared with females, males were older at diagnosis, more likely to be hormone receptor-positive and lymph node-positive disease, and more likely to have mastectomy. The proportion of males undergoing breast conserving surgery receiving radiotherapy was the only BreastSurgANZ KPI that was not met. Males were less likely to receive adjuvant chemotherapy than females using NCCN guidelines. CONCLUSION: Australian males with breast cancer account for 0.6% of breast cancer incidence and have similar clinico-pathological features as reported internationally. Overall, there is good compliance with the surgical KPIs, and adherence to NCCN guidelines for adjuvant systemic treatment is similar to previous international studies.

RESILIENCE: Phase III Randomized, Double-Blind Trial Comparing Sorafenib With Capecitabine Versus Placebo With Capecitabine in Locally Advanced or Metastatic HER2-Negative Breast Cancer.

INTRODUCTION: Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. In this randomized, double-blind, placebo-controlled phase III trial, we assessed first- or second-line capecitabine with sorafenib or placebo in patients with locally advanced/metastatic HER2-negative breast cancer resistant to a taxane and anthracycline and with known estrogen/progesterone receptor status. PATIENTS AND METHODS: A total of 537 patients were randomized to capecitabine 1000 mg/m2 orally twice per day for days 1 to 14 every 21 days with oral sorafenib 600 mg/d or placebo. The primary end point was progression-free survival (PFS). Patients were stratified according to hormone receptor status, previous chemotherapies for metastatic breast cancer, and geographic region. RESULTS: Treatment with sorafenib with capecitabine, compared with capecitabine with placebo, did not prolong median PFS (5.5 vs. 5.4 months; hazard ratio [HR], 0.973; 95% confidence interval [CI], 0.779-1.217; P = .811) or overall survival (OS; 18.9 vs. 20.3 months; HR, 1.195; 95% CI, 0.943-1.513; P = .140); or enhance overall response rate (ORR; 13.5% vs. 15.5%; P = .515). Any grade toxicities (sorafenib vs. placebo) included palmar-plantar erythrodysesthesia syndrome (PPES; 79.2% vs. 59.6%), diarrhea (47.3% vs. 37.8%), mucosal inflammation (15.4% vs. 6.7%), and hypertension (26.2% vs. 5.6%). Grade 3/4 toxicities included PPES (15.4% vs. 7.1%), diarrhea (4.2% vs. 6.4%), and vomiting (3.5% vs. 0.7%). CONCLUSION: The combination of sorafenib with capecitabine did not improve PFS, OS, or ORR in patients with HER2-negative advanced breast cancer. Rates of Grade 3 toxicities were higher in the sorafenib arm.

Final Results of the Randomized Phase II NorCap-CA223 Trial Comparing First-Line All-Oral Versus Taxane-Based Chemotherapy for HER2-Negative Metastatic Breast Cancer.

BACKGROUND: The purpose of this study was to evaluate the efficacy of 3 first-line chemotherapy combination regimens for HER2-negative metastatic breast cancer (mBC). PATIENTS AND METHODS: In this open-label, 3-arm, randomized phase II trial, patients were randomized to all-oral NORCAP (vinorelbine/capecitabine), GEMPAC (gemcitabine/paclitaxel), or GEMDOC (gemcitabine/docetaxel) as first-line chemotherapy for HER2-negative mBC. Stratification factors were center, previous (neo)adjuvant anthracycline, and age. The primary end point was disease control rate (DCR; complete or partial response, or stable disease for ≥3 months). RESULTS: The DCR was 73% (95% confidence interval [CI], 59-85) with NORCAP (36 of 49 patients), 78% (95% CI, 64-88) with GEMPAC (39 of 50 patients), and 80% (95% CI, 66-90) with GEMDOC (40 of 50 patients). Objective response rates were 33% (16 of 49 patients), 24% (12 of 50 patients), and 50% (25 of 50 patients), respectively; median progression-free survival was 7.6, 9.0, and 11.4 months, respectively. Median overall survival was 30 to 31 months with all regimens. The most common Grade ≥3 adverse event with each regimen was neutropenia (24 patients [50%], 23 patients [46%], and 43 patients [86%], respectively). The most common nonhematological Grade ≥3 adverse event was fatigue. Grade 2 alopecia occurred in 36 patients (72%) who received GEMPAC and 38 patients (76%) who received GEMDOC, but only 4 patients (8%) who received NORCAP. There was no evidence of a detrimental effect of NORCAP on quality of life. CONCLUSION: All-oral NORCAP is an active first-line chemotherapy regimen and might be offered as an alternative to first-line taxane-based therapy for HER2-negative mBC, particularly if patients wish to avoid alopecia or frequent intravenous administrations.

Challenges to effective cancer control in China, India, and Russia.

Cancer is one of the major non-communicable diseases posing a threat to world health. Unfortunately, improvements in socioeconomic conditions are usually associated with increased cancer incidence. In this Commission, we focus on China, India, and Russia, which share rapidly rising cancer incidence and have cancer mortality rates that are nearly twice as high as in the UK or the USA, vast geographies, growing economies, ageing populations, increasingly westernised lifestyles, relatively disenfranchised subpopulations, serious contamination of the environment, and uncontrolled cancer-causing communicable infections. We describe the overall state of health and cancer control in each country and additional specific issues for consideration: for China, access to care, contamination of the environment, and cancer fatalism and traditional medicine; for India, affordability of care, provision of adequate health personnel, and sociocultural barriers to cancer control; and for Russia, monitoring of the burden of cancer, societal attitudes towards cancer prevention, effects of inequitable treatment and access to medicine, and a need for improved international engagement.

Management of ErbB2-positive breast cancer: insights from preclinical and clinical studies with lapatinib.

The management of human epidermal growth factor receptor 2-positive (ErbB2+) breast cancer is challenging; patients with ErbB2+ breast tumors have more aggressive disease and a poor prognosis. The increasing incidence of breast cancer in Asia and the limitations of existing treatments pose additional challenges. In this review, we summarize the preclinical and clinical evidence that indicates how lapatinib, a novel inhibitor that targets the human epidermal growth factor receptor (ErbB1) and ErbB2 may help clinicians address four particularly challenging issues in the management of ErbB2+ breast cancer. These issues are: (i) trastuzumab therapy failure, (ii) development of central nervous system metastases, (iii) minimizing toxicity and (iv) selecting the most appropriate partners (chemotherapy and non-chemotherapy) for combination therapy with lapatinib. Lapatinib, in combination with chemotherapeutic agents, such as capecitabine, provides clinical benefits to patients with ErbB2+ breast cancer, including patients who develop progressive disease on trastuzumab. Lapatinib, in combination with non-chemotherapeutic agents, such as letrozole, may also provide a chemotherapy-free treatment option for postmenopausal patients with estrogen receptor-positive/ErbB2+ metastatic breast cancer. Encouraging results have also emerged regarding the synergistic effects of lapatinib in combination with other agents for the treatment of ErbB2+ breast cancer. Promising findings have also been reported for the use of lapatinib to prevent and treat central nervous system metastases. Collectively, these results indicate that the judicious use of lapatinib, an effective oral therapy with a manageable toxicity profile, can enhance the management of patients with ErbB2+ breast cancer.

Capecitabine and vinorelbine in metastatic breast cancer.

BACKGROUND: As anthracyclines and taxanes are frequently used in the adjuvant and first-line metastatic settings, capecitabine and vinorelbine are frequently used as monotherapy and in combination for metastatic breast cancer (MBC). In the absence of comparative, phase III data, retrospective analyses and cross-trial comparisons provide the only indication of the relative efficacy of these options. METHODS: We reviewed studies evaluating the 2 agents alone or in combination in MBC. RESULTS: We identified 6 capecitabine and 2 vinorelbine phase III trials, numerous phase II monotherapy studies and 35 phase I/II studies exploring capecitabine-vinorelbine combination therapy (1 with trastuzumab in HER2-positive MBC). CONCLUSION: For monotherapy, the limited, retrospective comparative evidence supported by consistent prospective data suggests that capecitabine is more effective than vinorelbine. Comorbidities, organ function tolerability, tumour biology and patient characteristics should also inform treatment choice. If combination therapy is deemed clinically appropriate, intravenous vinorelbine with capecitabine may be considered, potentially improving efficacy compared with monotherapy, but at the cost of increased toxicity. Randomised evaluation versus capecitabine monotherapy is ongoing. In contrast, cross-trial comparison suggests that addition of oral vinorelbine to capecitabine adds haematological toxicity without apparently improving efficacy in pretreated MBC. Data from small, single-arm, phase II studies in the first-line setting are more encouraging. In summary, the strongest clinical data support capecitabine monotherapy in the majority of patients. In certain populations, a capecitabine-vinorelbine combination may be appropriate but requires further validation in randomised trials.