The 4th International Consensus Conference for Breast Cancer in Young Women (BCY4) took place in October 2018, in Lugano, Switzerland, organized by the European School of Oncology (ESO) and the ...European Society of Medical Oncology (ESMO). Consensus recommendations for the management of breast cancer in young women were updated from BCY3 with incorporation of new evidence to inform the guidelines. Areas of research priorities were also identified. This article summarizes the ESO–ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).
•Breast cancer in young women should be treated based on stage and biology of disease.•Management of breast cancer in young women requires special considerations including psychological, reproductive and genetic.•Breast cancer in young women necessitates multi-disciplinary care at diagnosis, during treatment and during survivorship.
Patient-reported outcomes are integral in benefit–risk assessments of new treatment regimens. The PALOMA-2 study provides the largest body of evidence for patient-reported health-related quality of ...life (QOL) for patients with metastatic breast cancer (MBC) receiving first-line endocrine-based therapy (palbociclib plus letrozole and letrozole alone).
Treatment-naïve postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) MBC were randomized 2 : 1 to palbociclib plus letrozole (n=444) or placebo plus letrozole (n=222). Patient-reported outcomes were assessed at baseline, day 1 of cycles 2 and 3, and day 1 of every other cycle from cycle 5 using the Functional Assessment of Cancer Therapy (FACT)-Breast and EuroQOL 5 dimensions (EQ-5D) questionnaires.
As of 26 February 2016, the median duration of follow-up was 23months. Baseline scores were comparable between the two treatment arms. No significant between-arm differences were observed in change from baseline in FACT-Breast Total, FACT-General Total, or EQ-5D scores. Significantly greater improvement in pain scores was observed in the palbociclib plus letrozole arm (−0.256 versus −0.098; P=0.0183). In both arms, deterioration of FACT-Breast Total score was significantly delayed in patients without progression versus those with progression and patients with partial or complete response versus those without. No significant difference was observed in FACT-Breast and EQ-5D index scores in patients with and without neutropenia.
Overall, women with MBC receiving first-line endocrine therapy have a good QOL. The addition of palbociclib to letrozole maintains health-related QOL and improves pain scores in treatment-naïve postmenopausal patients with ER+/HER2− MBC compared with letrozole alone. Significantly greater delay in deterioration of health-related QOL was observed in patients without progression versus those who progressed and in patients with an objective response versus non-responders.
ClinicalTrials.gov: NCT01740427 (https://clinicaltrials.gov/ct2/show/NCT01740427)
We dedicate this manuscript in memory of a dear friend and colleague Bella Kaufman.
The fifth International Consensus Symposium for Breast Cancer in Young Women (BCY5) took place virtually in October ...2020, organized by the European School of Oncology (ESO) and the European Society of Medical Oncology (ESMO). Consensus recommendations for the management of breast cancer in young women were updated from BCY4 with incorporation of new evidence to inform the guidelines. Areas of research priorities as well as specificities in different geographic and minority populations were identified. This manuscript summarizes the ESO–ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).
•Breast cancer in young women encompasses unique treatment and survivorship considerations.•Fertility, ovarian function suppression and premature menopause are major issues that need to be addressed.•The presence of a germline pathogenic variant impacts risk reduction measures, local management and systemic therapy.•Research on how new systemic therapies impact fertility and ovarian function is urgently needed.
Research needs in breast cancer Cardoso, F.; Harbeck, N.; Barrios, C.H. ...
Annals of oncology,
02/2017, Letnik:
28, Številka:
2
Journal Article
Recenzirano
Odprti dostop
New research questions emerge as medical needs continue to evolve and as we improve our understanding of cancer biology and treatment of malignancies. Although significant advances have been made in ...some areas of breast cancer research resulting in improvements in therapies and outcomes over the last few decades, other areas have not benefited to the same degree and we continue to have many gaps in our knowledge. This article summarizes the 12 short and medium-term clinical research needs in breast cancer deemed as priorities in 2016 by a panel of experts, in an attempt to focus and accelerate future research in the most needed areas: (i) de-escalate breast cancer therapies in early breast cancer without sacrificing outcomes; (ii) explore optimal adjuvant treatment durations; (iii) develop better tools and strategies to identify patients with genetic predisposition; (iv) improve care in young patients with breast cancer; (v) develop tools to speed up drug development in biomarker-defined populations; (vi) identify and validate targets that mediate resistance to chemotherapy, endocrine therapy and anti-HER2 therapies; (vii) evaluate the efficacy of local-regional treatments for metastatic disease; (viii) better define the optimal sequence of treatments in the metastatic setting; (ix) evaluate the clinical impact of intra-patient heterogeneity (intra-tumor, inter-tumor and inter-lesion heterogeneity); (x) better understand the biology and identify new targets in triple-negative breast cancer; (xi) better understand immune surveillance in breast cancer and further develop immunotherapies; and (xii) increase survivorship research efforts including supportive care and quality of life.
Invasive breast cancer is a heterogeneous disease in its presentation, pathological classification and clinical course. However, there are more than a dozen variants which are less common but still ...very well defined by the World Health Organization (WHO) classification. The rarity of many of these neoplasms does not allow large or randomized studies to define the optimal treatment. Many of the descriptions of these cancers are from case reports and small series. Our review brings updated information on 16 epithelial subtypes as classified by the WHO system with a very concise histopathology description and parameters helpful in the clinic. The aim of our review is to provide a tool for breast cancer caregivers which will enable a better understanding of the disease and its optimal approach to therapy. This may also stand as a clinical framework for a future understanding of these rarer breast cancers when gene analysis work is reported.
Little is known about the correlations between tumor markers (TMs), breast cancer subtypes, site(s) of metastasis and prognosis.
Women diagnosed with metastatic breast cancer were included. Breast ...cancer subtypes were defined as LuminalA, LuminalB, LuminalHer2, Her2, Basal and non-Basal triple negative (TN). Levels of elevation of TM values cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA 125) among the subtypes were analyzed. Site(s) of metastasis and outcomes were captured.
Eight hundred and ten patients were included. Luminal subtypes were associated with an elevation in at least one TM: 90.8% of LuminalHer2+, 90% of LuminalB and 88.6% of LuminalA. TMs were less frequently elevated in Basal (74.1%) and non-Basal TN (71.4%) cases (P < 0.001). CA 15-3 was the most frequently elevated TM. The incidence of TM elevation did not differ between patients with solitary versus multiple metastatic sites. Breast cancer-specific survival (BCSS) was significantly worse for patients with elevated TMs (P = 0.001).
TM elevation of CA 15-3, CEA and/or CA 125 was documented in the majority of patients with metastatic breast cancer with CA 15-3 occurring most commonly. Luminal subtypes expressed elevated TMs significantly more frequently compared with the non-Luminal groups. TM elevation was not different between the different sites of metastasis. Overall, elevated TMs predicted a worse BCSS.
The PARP inhibitor olaparib (Lynparza™) demonstrates antitumor activity in women with relapsed ovarian cancer and a germline BRCA1/2 mutation (gBRCAm). Data from olaparib monotherapy trials were used ...to explore the treatment effect of olaparib in patients with gBRCAm ovarian cancer who had received multiple lines of prior chemotherapy.
This analysis evaluated pooled data from two phase I trials NCT00516373 (study 2); NCT00777582 (study 24) and four phase II trials NCT00494442 (study 9); NCT00628251 (study 12); NCT00679783 (study 20); NCT01078662 (study 42) that recruited women with relapsed ovarian, fallopian tube or peritoneal cancer. All patients had a documented gBRCAm and were receiving olaparib 400 mg monotherapy twice daily (capsule formulation) at the time of relapse. Objective response rate (ORR) and duration of response (DoR) were evaluated using original patient outcomes data for patients with measurable disease at baseline.
Of the 300 patients in the pooled population, 273 had measurable disease at baseline, of whom 205 (75%) had received ≥3 lines of prior chemotherapy. In the pooled population, the ORR was 36% 95% confidence interval (CI) 30–42 and the median DoR was 7.4 months (95% CI 5.7–9.1). The ORR among patients who had received ≥3 lines of prior chemotherapy was 31% (95% CI 25–38), with a DoR of 7.8 months (95% CI 5.6–9.5). The safety profile of olaparib was similar in patients who had received ≥3 lines of prior chemotherapy compared with the pooled population; grade ≥3 adverse events were reported in 54% and 50% of patients, respectively.
Durable responses to olaparib were observed in patients with relapsed gBRCAm ovarian cancer who had received ≥3 lines of prior chemotherapy.
NCT00516373; NCT00494442; NCT00628251; NCT00679783; NCT00777582; NCT01078662.
Purpose
In the initial PALOMA-2 (NCT01740427) analysis with median follow-up of 23 months, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) in women with estrogen ...receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) hazard ratio (HR) 0.58;
P
< 0.001. Herein, we report results overall and by subgroups with extended follow-up.
Methods
In this double-blind, phase 3 study, post-menopausal women with ER+/HER2− ABC who had not received prior systemic therapy for their advanced disease were randomized 2:1 to palbociclib-letrozole or placebo-letrozole. Endpoints include investigator-assessed PFS (primary), safety, and patient-reported outcomes (PROs).
Results
After a median follow-up of approximately 38 months, median PFS was 27.6 months for palbociclib–letrozole (
n
= 444) and 14.5 months for placebo-letrozole (
n
= 222) (HR 0.563; 1-sided
P
< 0.0001). All subgroups benefited from palbociclib treatment. The improvement of PFS with palbociclib-letrozole was maintained in the next 2 subsequent lines of therapy and delayed the use of chemotherapy (40.4 vs. 29.9 months for palbociclib–letrozole vs. placebo-letrozole). Safety data were consistent with the known profile. Patients’ quality of life was maintained.
Conclusions
With approximately 15 months of additional follow-up, palbociclib plus letrozole continued to demonstrate improved PFS compared with placebo plus letrozole in the overall population and across all patient subgroups, while the safety profile remained favorable and quality of life was maintained. These data confirm that palbociclib-letrozole should be considered the standard of care for first-line therapy in patients with ER+/HER2− ABC, including those with low disease burden or long disease-free interval. Sponsored by Pfizer; ClinicalTrials.gov: NCT01740427.
Abstract Purpose The primary purpose of this study was to measure the impact of the 21-gene Recurrence Score® result on systemic treatment recommendations and to perform a prospective health economic ...analysis in stage I–II, node-negative, oestrogen receptor positive (ER+) breast cancer. Methods Consenting patients with ER+ node negative invasive breast cancer and their treating medial oncologists were asked to complete questionnaires about treatment preferences, level of confidence in those preferences and a decisional conflict scale (patients only) after a discussion of their diagnosis and risk without knowledge of the Recurrence Score. At a subsequent visit, the assay result and final treatment recommendations were discussed prior to both parties completing a second set of questionnaires. A Markov health state transition model was constructed, simulating the costs and outcomes experienced by a hypothetical ‘assay naïve’ population and an ‘assay informed’ population. Results One hundred and fifty-six patients across two cancer centres were enrolled. Of the 150 for whom successful assay results were obtained, physicians changed their chemotherapy recommendations in 45 cases (30%; 95% confidence interval (CI) 22.8–38.0%); either to add (10%; 95% CI 5.7–16.0%) or omit (20%; 95% CI 13.9–27.3%) adjuvant chemotherapy. There was an overall significant improvement in physician confidence post-assay ( p < 0.001). Patient decisional conflict also significantly decreased following the assay ( p < 0.001). The simulation model found an incremental cost-effectiveness ratio of Canadian Dollars (CAD) $6630/quality-adjusted life years (QALY). Conclusion Within the context of a publicly funded health care system, the Recurrence Score assay significantly affects adjuvant treatment recommendations and is cost effective in ER+ node negative breast cancer.
This report assesses the efficacy and safety of palbociclib plus endocrine therapy (ET) in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast ...cancer (ABC) with or without visceral metastases.
Pre- and postmenopausal women with disease progression following prior ET (PALOMA-3; N=521) and postmenopausal women untreated for ABC (PALOMA-2; N=666) were randomized 2:1 to ET (fulvestrant or letrozole, respectively) plus palbociclib or placebo. Progression-free survival (PFS), safety, and patient-reported quality of life (QoL) were evaluated by prior treatment and visceral involvement.
Visceral metastases incidence was higher in patients with prior resistance to ET (58.3%, PALOMA-3) than in patients naive to ET in the ABC setting (48.6%, PALOMA-2). In patients with prior resistance to ET and visceral metastases, median PFS (mPFS) was 9.2months with palbociclib plus fulvestrant versus 3.4months with placebo plus fulvestrant hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.35–0.61, and objective response rate (ORR) was 28.0% versus 6.7%, respectively. In patients with nonvisceral metastases, mPFS was 16.6 versus 7.3months, HR 0.53; 95% CI 0.36–0.77. In patients with visceral disease and naive to ET in the advanced disease setting, mPFS was 19.3months with palbociclib plus letrozole versus 12.9months with placebo plus letrozole (HR 0.63; 95% CI 0.47–0.85); ORR was 55.1% versus 40.0%; in patients with nonvisceral disease, mPFS was not reached with palbociclib plus letrozole versus 16.8months with placebo plus letrozole (HR 0.50; 95% CI 0.36–0.70). In patients with prior resistance to ET with visceral metastases, palbociclib plus fulvestrant significantly delayed deterioration of QoL versus placebo plus fulvestrant, whereas patient-reported QoL was maintained with palbociclib plus letrozole in patients naive to endocrine-based therapy for ABC.
Palbociclib plus ET prolonged mPFS in patients with visceral metastases, increased ORRs, and in patients previously treated for ABC, delayed QoL deterioration, presenting a standard treatment option among patients with visceral metastases amenable to endocrine-based therapy.
NCT01942135, NCT01740427
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