Current Management and Future Perspectives of Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer.

OBJECTIVES: An overview of the best therapeutic approaches for the management of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer is provided, and emerging treatment advances are discussed. Key nursing considerations and the role of the nurse in the provision of optimal care are explored. DATA SOURCES: Data sources include peer-reviewed articles sourced in electronic databases. CONCLUSION: With a multitude of current and emerging treatments for the management of hormone receptor-positive, HER2-negative advanced breast cancer, patients with this subtype have improved overall survival. It is essential that specialist nurses holistically support patients; this will ensure treatment adherence, leading to enhanced longevity and quality of life. IMPLICATIONS FOR NURSING PRACTICE: Nurses play an important role in patient education and the early identification and management of treatment toxicities. Nurses also need to monitor and facilitate adherence by identifying barriers and implementing strategies to overcome them, ultimately improving patient outcomes.

Survival Disparities in US Black Compared to White Women with Hormone Receptor Positive-HER2 Negative Breast Cancer.

Black women in the US have significantly higher breast cancer mortality than White women. Within biomarker-defined tumor subtypes, disparate outcomes seem to be limited to women with hormone receptor positive and HER2 negative (HR+/HER2-) breast cancer, a subtype usually associated with favorable prognosis. In this review, we present data from an array of studies that demonstrate significantly higher mortality in Black compared to White women with HR+/HER2-breast cancer and contrast these data to studies from integrated healthcare systems that failed to find survival differences. Then, we describe factors, both biological and non-biological, that may contribute to disparate survival in Black women.

A Retrospective Analysis of Metronomic Cyclophosphamide, Methotrexate, and Fluorouracil (CMF) Versus Docetaxel and Cyclophosphamide (TC) as Adjuvant Treatment in Early Stage, Hormone Receptor Positive, HER2 Negative Breast Cancer.

BACKGROUND: Anthracycline and taxane-based doublets have largely replaced cyclophosphamide, methotrexate, and fluorouracil (CMF) as preferred regimens in the adjuvant treatment of breast cancer. Metronomic CMF is associated with improved tolerability over anthracycline or taxane-based regimens. Previously, there have been no direct comparisons between taxane-based regimens and CMF. MATERIALS AND METHODS: We performed a retrospective review of 98 breast cancer patients treated at the Seattle Cancer Care Alliance from February 2015 through December 2018 that received either metronomic CMF or docetaxel and cyclophosphamide (TC) as adjuvant therapy for early-stage, hormone receptor-positive/human epidermal growth factor receptor-2 negative (HR+/HER2-) breast cancer. The primary outcome assessed was disease-free survival (DFS). Secondary outcomes included overall survival (OS), dose intensity, and adverse effects. RESULTS: With an average follow-up of 35.9 and 28.2 months for CMF and TC, respectively, there was no significant difference in DFS or OS between the chemotherapy regimens. DFS at 3 years was 96.7% vs. 94.3% and OS 96.7% vs. 100% for CMF and TC, respectively. There were more dose delays in the CMF group, but on average, patients receiving either regimen achieved a dose intensity ≥85%. There was a trend towards increased hospitalization or emergency department utilization (23.1% vs. 10.6%) and Grade 4 toxicities (9.6% vs. 4.3%) with TC vs. CMF. CONCLUSION: Metronomic CMF offers equivalent survival outcomes to TC and remains a viable option in the adjuvant treatment of HR+/HER2- breast cancer. There was a trend towards increased Grade 4 toxicities and hospitalizations with TC, suggesting that metronomic CMF may offer a more tolerable treatment option while maintaining excellent disease outcomes.

Patient-Reported Outcomes From Phase III Neoadjuvant Systemic Trial Comparing Neoadjuvant Chemotherapy With Neoadjuvant Endocrine Therapy in Pre-Menopausal Patients With Estrogen Receptor-Positive and HER2-Negative, Lymph Node-Positive Breast Cancer.

We aimed to evaluate the patient-reported outcomes (PROs) in a prospective phase III clinical trial, comparing neoadjuvant endocrine therapy (NET) with conventional neoadjuvant chemotherapy (NCT) in patients with hormone status positive, lymph node-positive premenopausal breast cancer (NCT01622361). The patients were randomized prospectively to either 24 weeks of NCT with adriamycin plus cyclophosphamide followed by taxane or NET with gonadotropin-releasing hormone agonist and tamoxifen. The patients were examined at the surgery unit of a large tertiary care hospital with a comprehensive cancer center. PROs were assessed on the first day of the trial (day 1, baseline) and at the end of treatment, using the breast cancer module of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 23 (EORTC QLQ BR23). One hundred and eighty-seven patients were randomly assigned to chemotherapy (n=95) or endocrine therapy (n=92), and 174 patients completed 24 weeks of the neoadjuvant treatment period (n=87, in each group). Baseline scores were similar between the groups. After treatment, there were no statistically significant differences in the function scales, including body image, sexual functioning, and sexual enjoyment between the groups, although the endocrine treatment group showed a significant improvement in the future perspective (hazard ratio, 8.3; 95% confidence interval, 1.72-18.38; P = 0.021). Similarly, there were no statistically significant differences in the symptom scales between the groups, including adverse effects of systemic therapy, breast symptoms, arm symptoms, and upset about hair loss. In conclusion, overall PROs were similar in both treatment groups, except for "future perspective," which was significantly better in the NET group than in the NCT group. CLINICAL TRIAL REGISTRATION: ClinicalTrials.Gov, identifier NCT01622361.

Disparities in Guideline-Concordant Initial Systemic Treatment in Women with HER2-Negative Metastatic Breast Cancer: A SEER-Medicare Analysis.

BACKGROUND: Data on guideline-concordant initial systemic treatment among women with HER2-negative metastatic breast cancer (MBC) are limited. We determined the proportion of women with HER2-negative MBC who received guideline-concordant treatment and the extent to which independent variables explained differences in guideline-concordant treatment by hormone receptor (HR) status. METHODS: We conducted a retrospective cohort study using the SEER-Medicare database. We included women age >65 years diagnosed with HER2-negative MBC during 2010-2013. We used the National Comprehensive Cancer Network treatment guidelines to determine guideline-concordant initial treatment within the first 6 months of a cancer diagnosis. We conducted a multivariable logistic regression to identify the significant predictors of guideline-concordant treatment and a non-linear decomposition method to examine disparities by HR status. RESULTS: Among 1089 eligible women, 72.3% received guideline-concordant treatment. Compared to women who did not receive guideline-concordant treatment, women who received guideline-concordant treatment were more like to be comparatively older (p<0.05), married (p=0.0171), resided in areas with higher proportion of people age ≥25 years with at least four years of college education, and had positive HR status (p<0.0001). Approximately 8% of the disparity in guideline-concordant treatment by HR status was explained by their observed characteristics. Need-related factors explained the highest proportion (66.9%) of the disparity. CONCLUSION: Our findings indicate improvement of care for older women, who are single/divorced, have negative HR status, and who live in area with lower education levels. Unexplained disparities in guideline-concordant treatment by HR status can be attributed to patient preferences for treatment, physician-level factors, and perceptions.

COVID-19 risk in breast cancer patients receiving CDK4/6 inhibitors: literature data and a monocentric experience.

Substantial changes in the management of cancer patients have been required worldwide in response to the COVID-19 pandemic. Beyond the due details on the primitive cancer site and setting at diagnosis, these latter adaptions are most commonly exemplified by a significant reduction in the screening of asymptomatic subjects, delays in elective surgery and radiotherapy for primary tumors, and dose reductions and/or delays in systemic therapy administration. Advanced breast cancer patients with hormonal receptor positive, HER2 negative tumors are usually treated with endocrine therapy combined with CDK 4/6 inhibitors as first- and second-line treatment. During the pandemic, experts' recommendations have suggested the omission or delay of CDK 4/6 inhibitors delivery, or a careful evaluation of their real need due to the hypothesized increased risk of SARS-Cov-2 infection and disease possibly related to neutropenia. The inherent literature is sparse and inconsistent. We herein present data on the use of CDK 4/6 inhibitors during the pandemic. The evidence reported punctually reflects the experience matured at our Institution, a comprehensive cancer centre, on the topic of interest.

Psychosocial aspects and life project disruption in young women diagnosed with metastatic hormone-sensitive HER2-negative breast cancer.

Metastatic breast cancer (MBC) diagnosis in young women negatively impacts on quality of life (QoL) and daily activities, disrupting their life project and forcing them to face new psychosocial challenges. The recently published results on the improvement of the overall survival of pre- or perimenopausal women with hormone-receptor-positive, HER2-negative MBC treated with CDK4/6 inhibitors plus endocrine therapy, while preserving, and in some items improving their QoL, will change the landscape of the management of this patient population. Their extended survival and potential improvement in QoL will, therefore, modify their specific needs in terms of psychosocial support. The complexity of the care of young women with MBC is described herein, based on an extensive literature review. Further research about the specific psychosocial requirements of these women and a new multidisciplinary holistic approach is paramount to properly address their concerns and preferences. The communication with and support of their partners, parents and children is an important factor affecting the QoL of these patients. Altogether, a multidisciplinary care, open communication and personalized support is required to address the psychosocial implications of the new prognostic expectations on these patients with the incorporation of new targeted therapies.

Endocrine therapy or chemotherapy as first-line therapy in hormone receptor-positive HER2-negative metastatic breast cancer patients.

BACKGROUND: For hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2-) negative metastatic breast cancer (MBC), international guidelines recommend endocrine therapy as first-line treatment, except in case of 'visceral crisis'. In the latter case, chemotherapy is preferred. Few studies have compared these two strategies. We used the Epidemiological Strategy and Medical Economics (ESME) programme, UNICANCER, a large national observational database (NCT03275311), to address this question. METHODS: All patients who initiated treatment for a newly diagnosed HR+ HER2-negative MBC between January 2008 and December 2014 in any of the 18 French Comprehensive Cancer Centers participating to ESME were selected. Patients should be aromatase inhibitor (AI)-sensitive (no previous AI or relapse occurring more than 1 year after last adjuvant AI). Objectives of the study were evaluation of progression-free and overall survival (OS) according to the type of first-line treatment adjusted on main prognostic factors using a propensity score. RESULTS: Six thousand two hundred sixty-five patients were selected: 2733 (43.6%) received endocrine therapy alone, while 3532 (56.4%) received chemotherapy as first-line therapy. Among the latter, 2073 (58.7%) received maintenance endocrine therapy. Median OS was 60.78 months (95% confidence interval [CI], 57.16-64.09) and 49.64 months (95% CI, 47.31-51.64; p < 0.0001) for patients receiving endocrine therapy alone and chemotherapy ± maintenance endocrine therapy, respectively. However, this difference was not significant after adjusting on the propensity score (hazard ratio: 0.943, 95% CI 0.863-1.030, p = 0.19). CONCLUSION: In this large retrospective cohort of patients with AI-sensitive metastatic luminal BC, OS was similar, whether first-line treatment was chemotherapy or endocrine therapy. In agreement with international guidelines, endocrine therapy should be the first choice for first-line systemic treatment for MBC in the absence of visceral crisis.

Neoadjuvant everolimus plus letrozole versus fluorouracil, epirubicin and cyclophosphamide for ER-positive, HER2-negative breast cancer: study protocol for a randomized pilot trial.

BACKGROUND: The response to neoadjuvant chemotherapy (NAC) varies by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) statuses, with responses being lower in ER-positive, HER2-negative tumors as compared with ER-negative, HER2-positive or triple-negative tumors. Neoadjuvant endocrine therapy (NET) is an attractive alternative to NAC for ER-positive, HER2-negative cancer. However, a prior trial comparing NET with standard NAC in ER-positive tumor showed that the difference of response was not significant. Studies demonstrated that the mTOR inhibitor everolimus could sensitize breast tumors to endocrine therapy. A pilot open-label, randomized trial has been designed to evaluate the feasibility, efficacy and tolerability of neoadjuvant everolimus plus letrozole versus NAC in treating postmenopausal women with ER-positive, HER2-negative breast cancer. METHODS: Forty postmenopausal women with non-metastatic ER-positive, HER2-negative invasive breast cancer with a primary tumor > 2 cm or positive axillary lymph node(s) proved by biopsy will be randomly (1:1) enrolled from Sun Yat-Sen Memorial Hospital to receive neoadjuvant everolimus plus letrozole for 18 weeks or fluorouracil, epirubicin plus cyclophosphamide (FEC) for six cycles before surgery. Primary outcome is the feasibility of the trial. Secondary outcome measures include ultrasound response rate, pathological complete response rate, breast-conserving surgery rate, toxicities, and changes in the percentages of peripheral blood CD4+ T cells, CD8+ T cells, T helper cells, regulatory T cells, and NK cells. DISCUSSION: This is the first study to determine the feasibility, efficacy and tolerability of head-to-head neoadjuvant everolimus plus letrozole versus neoadjuvant FEC in treating postmenopausal women with ER-positive, HER2-negative breast cancer. The trial will provide evidence to assess the feasibility of a future multicenter, randomized controlled trial, and will provide valuable clinical data of the immunoregulatory effect of everolimus in breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov registry, ID: NCT02742051 . Registered on 7 April 2016.

Prevalence of Circulating Tumor Cells After Adjuvant Chemotherapy With or Without Anthracyclines in Patients With HER2-negative, Hormone Receptor-positive Early Breast Cancer.

BACKGROUND: Use of anthracycline-based chemotherapy in patients with early breast cancer (EBC) has been well-established but is often associated with cardiotoxicity. Based on data suggesting a limited benefit of anthracyclines in human epidermal growth factor receptor 2 (HER2)-negative patients, the Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as well as Life Style Intervention Strategies (SUCCESS) C study randomized patients to either anthracycline-containing or anthracycline-free chemotherapy. Given the proven prognostic value of circulating tumor cells (CTCs) in EBC, we compared the prevalence of CTCs after chemotherapy between both treatment arms for a preliminary efficacy assessment. METHODS: The SUCCESS C trial (NCT00847444) is an open-label, phase III study randomizing 3547 patients with HER2-negative EBC to either 3 cycles of epirubicin, 5-fluorouracil, and cyclophosphamide followed by 3 cycles of docetaxel (FEC-DOC) or 6 cycles of docetaxel and cyclophosphamide (DOC-C). CTC status was prospectively evaluated in hormone receptor-positive patients at the time of last chemotherapy cycle using the US Food and Drug Administration-approved CellSearch System (Janssen Diagnostics). RESULTS: Data on CTC status were available for 1766 patients. Overall, CTCs were found in 221 (12.5%) patients. Univariate analyses revealed that presence of CTCs at time of last chemotherapy cycle was not significantly associated with tumor or patient characteristics (all P > .1). There was no significant difference with respect to presence of CTCs between patients randomized to FEC-DOC or DOC-C (11.5% vs. 13.6%; P = .18). CONCLUSIONS: The comparable prevalence of CTCs at the time of last chemotherapy cycle may indicate that anthracycline-free chemotherapy is equally effective to anthracycline-containing chemotherapy in HER2-negative, hormone receptor-positive EBC. However, efficacy data from the final survival analysis of SUCCESS C have to be awaited to confirm these preliminary findings.

Sorafenib Plus Ixabepilone as First-Line Treatment of Metastatic HER2-Negative Breast Cancer: A Sarah Cannon Research Institute Phase I/II Trial.

BACKGROUND: The purposes of the present phase I/II trial were (1) to define tolerable doses of ixabepilone and sorafenib when used in combination and (2) to evaluate the efficacy and toxicity of this combination in the treatment of patients with human epidermal growth factor receptor-negative metastatic breast cancer (MBC). PATIENTS AND METHODS: The eligible patients had human epidermal growth factor receptor-negative MBC and had not received previous chemotherapy in the metastatic setting. All patients received ixabepilone intravenously on day 1 of each 21-day treatment cycle; sorafenib was administered orally twice daily. Patients in phase II received the maximum doses identified in phase I. The patients were reevaluated after the completion of 3 treatment cycles; treatment continued until disease progression or intolerable toxicity. A total of 67 patients were required in phase II to demonstrate increased median progression-free survival from 4.2 to 6.2 months (90% power, α = 0.05). RESULTS: Ten patients entered the phase I portion; the maximum tolerated doses were ixabepilone 32 mg/m(2) and sorafenib 400 mg orally twice daily. A total of 76 patients were treated at the phase II dose. The median progression-free survival was 4.8 months (95% confidence interval, 3.5-6.3 months). The overall response rate was 37%. The regimen was difficult to tolerate for many patients; 20 patients discontinued because of toxicity, and dose reductions were frequent. The common toxicities included neutropenia, fatigue, rash, and neuropathy. CONCLUSION: The combination of ixabepilone and sorafenib was poorly tolerated as first-line treatment of patients with MBC. The activity of the combination was similar to the activity previously reported with single-agent ixabepilone or taxanes. Further development of this combination is not recommended.