Survival Outcomes and Care Equity among Patients with Advanced Breast Cancer in Auckland, New Zealand.

Aim: The Auckland Advanced Breast Cancer Review (AABC) was a review of patients diagnosed with advanced inoperable/metastatic breast cancer (ABC) within the Auckland region of New Zealand, commissioned in response to a Breast Cancer Registry report (BCFNZR) that showed poor and inequitable survival outcomes. The review was aimed at assessing equity of care and identifying healthcare delivery gaps for patients with ABC in the Auckland region. Method: In this retrospective study, patients living within the Auckland region, diagnosed with ABC between the 1st January 2013 to the 31st December 2015 were identified from the Breast Cancer Registry. Data censorship date was 30th January 2019 to allow a minimum of 3 years of follow-up. Demographic, diagnostic, treatment, and survival data were extracted from electronic records for statistical analysis. Results: Of the 388 patients that met inclusion criteria for this study, median overall survival (medOS) was 18.9 months in the total population, with no difference between patients with de novo metastatic disease (dnMBC -18.9 m) and recurrent metastatic disease (rMBC -18.7 m). No statistically significant differences in medOS was found amongst Maori (16.2 m), Pacific People (17.3 m), and NZ European (18.9 m) or when patients were stratified according domicile district health board. Median number of lines of systemic treatment was two, with similar treatment exposure between ethnic groups. Conclusion: While treatment uptake and survival outcomes were generally comparable across ethnicity and district health boards, dnMBC survival outcomes were considerably poorer than expected, earmarking this subset of patients with ABC for more in-depth research.

Homologous Recombination Deficiency and Platinum-Based Therapy Outcomes in Advanced Breast Cancer.

Purpose: Recent studies have identified mutation signatures of homologous recombination deficiency (HRD) in over 20% of breast cancers, as well as pancreatic, ovarian, and gastric cancers. There is an urgent need to understand the clinical implications of HRD signatures. Whereas BRCA1/2 mutations confer sensitivity to platinum-based chemotherapies, it is not yet clear whether mutation signatures can independently predict platinum response.Experimental Design: In this observational study, we sequenced tumor whole genomes (100× depth) and matched normals (60×) of 93 advanced-stage breast cancers (33 platinum-treated). We computed a published metric called HRDetect, independently trained to predict BRCA1/2 status, and assessed its capacity to predict outcomes on platinum-based chemotherapies. Clinical endpoints were overall survival (OS), total duration on platinum-based therapy (TDT), and radiographic evidence of clinical improvement (CI).Results: HRDetect predicted BRCA1/2 status with an area under the curve (AUC) of 0.94 and optimal threshold of 0.7. Elevated HRDetect was also significantly associated with CI on platinum-based therapy (AUC = 0.89; P = 0.006) with the same optimal threshold, even after adjusting for BRCA1/2 mutation status and treatment timing. HRDetect scores over 0.7 were associated with a 3-month extended median TDT (P = 0.0003) and 1.3-year extended median OS (P = 0.04).Conclusions: Our findings not only independently validate HRDetect, but also provide the first evidence of its association with platinum response in advanced breast cancer. We demonstrate that HRD mutation signatures may offer clinically relevant information independently of BRCA1/2 mutation status and hope this work will guide the development of clinical trials. Clin Cancer Res; 23(24); 7521-30. ©2017 AACR.

Risk of Recurrence or Contralateral Breast Cancer More than 5 Years After Diagnosis of Hormone Receptor-Positive Early-Stage Breast Cancer.

BACKGROUND: Three large studies have shown a survival benefit from 10 years of adjuvant hormone therapy (AHT). We evaluated the risk of an event 5 years after the initial breast cancer (BC) diagnosis and identified the prognostic factors to assist clinicians considering extended AHT. PATIENTS AND METHODS: Patients newly referred to the BC Cancer Agency with stage I to III estrogen receptor-positive BC diagnosed from 1989 to 2004 who had undergone AHT were identified by the BC Cancer Agency's Breast Cancer Outcomes Unit. Cases with recurrence, death, or contralateral BC occurring within the first 5 years were excluded. The 10-year event-free survival (EFS) and 95% confidence intervals (CIs) were calculated using the Kaplan-Meier method. This provided estimates of recurrence risk after the fifth year following the diagnosis. The histopathologic and age variables were examined for prognostic value by univariate analysis. RESULTS: Within our cohort, 6615 women were postmenopausal and 1886 were premenopausal at the BC diagnosis. The median follow-up period was 11 years. The 10-year EFS for women aged < 50 years with stage I, II, and III disease was 94.8% (95% CI, 92.8%-96.3%), 88.3% (95% CI, 86.0%-90.2%), and 80.4% (95% CI, 73.6%-85.6%), respectively. Among women aged ≥ 50 years, the corresponding EFS rates were 94.8% (95% CI, 93.8%-95.6%), 86.3% (95% CI, 85.0%-87.5%), and 73.8% (95% CI, 69.1%-77.8%). EFS varied significantly by grade. The 10-year recurrence risk was < 10% with stage I cancer (any grade) and for stage II (node-negative and node-positive), grade I cancer. CONCLUSION: Our data have identified BCs associated with a very low recurrence risk 5 to 10 years after diagnosis, providing women with such cancers confidence about a decision to discontinue AHT after 5 years.

New agents in locally advanced breast cancer.

PURPOSE OF REVIEW: Sequential anthracycline/taxane regimens are routinely used as neoadjuvant therapy (NAT) for locally advanced breast cancer. Unfortunately, the majority of patients do not achieve a pathological complete response (pCR). Efforts to improve pCR rates include the addition of novel targeted agents. The purpose of this article is to review recent developments in this area and to demonstrate the clinical and research advantages of a neoadjuvant platform for the evaluation of novel targeted therapy. RECENT FINDINGS: Dual human epidermal growth factor 2 (HER2)-targeting concurrent with chemotherapy has demonstrated superiority over chemotherapy with trastuzumab alone. Bevacizumab appears to have a modest effect on pCR rates and its role in neoadjuvant treatment remains uncertain. Despite promising preclinical signals, mTOR inhibition in combination with chemotherapy has yet to yield a benefit in the neoadjuvant setting and trials are ongoing. In contrast, mTOR inhibition in combination with endocrine therapy has demonstrated potential as NAT. SUMMARY: Dual HER2-targeting considerably improves pCR rates. Thus, far incorporation of non-HER2 targeted agents has been less successful. NAT provides an opportunity to evaluate novel agents, and thereby assist the development of a rationale adjuvant strategy, and facilitates the collection of samples for correlative research into breast cancer biology and predictive biomarkers/pathways.

Treatment algorithms for hormone receptor-positive advanced breast cancer: applying the results from recent clinical trials into daily practice­insights, limitations, and moving forward.

Hormone receptor-positive (HR+) breast cancer is the most prevalent subtype of breast cancer in both early- and advanced-stage disease. Thus, the treatment of HR+ breast cancer has had the greatest global influence in improving clinical outcomes overall. Although the first-line metastatic breast cancer (MBC) trials comparing a third-generation aromatase inhibitor (AI) to tamoxifen have favored the AI, one of the challenges in translating these findings into clinical practice stems from the influence of prior adjuvant endocrine therapy, particularly the increasing use of adjuvant AIs today, on the choice of endocrine agent in the advanced setting because of the development of acquired resistance. Because the majority of patients enrolled into these studies were either endocrine-treatment naïve or exposed to tamoxifen only, the "real-life" applicability of the evidence is unclear. Because a superior dose of the selective estrogen receptor (ER) downregulator fulvestrant has now been established, its role as first-line therapy is being re-established. We are now starting to see the promise realized with blocking cross-talking growth factor pathways in addition to the ER pathway. The greatest efficacy is seen with the mammalian target of rapamycin (mTOR) inhibitor everolimus in combination with exemestane and, perhaps to a lesser extent, anti-HER2-directed therapy in combination with an AI. Future gains will likely involve a greater understanding of the redundancy and compensation induced by blocking these pathways, trials involving blocking multiple pathways in addition to hormonal agents, and the molecular interrogation of the individual's tumor in search of predictive biomarkers and "actionable" genomic aberrations.