Positive Early Breast Cancer Research Articles

HER2 copy number quantification in primary tumor and cell-free DNA provides additional prognostic information in HER2 positive early breast cancer.

BackgroundThe quantitative relationship between HER2 copy number and prognosis in HER2 positive adjuvant setting remain controversial, and few studies have focused on adjuvant setting to illustrate the potential clinical relevance of HER2 in cfDNA. Our study aim to develop a novel method in HER2 quantification and explore the relationship between HER2 copy number in primary tumors or cfDNA and prognosis in HER2 positive early breast cancer.MethodsTwo hundred and two patients with early breast cancer were prospectively included in a study where primary tumors, matching non-cancer breast tissue, corresponding plasma, and the plasma from 20 healthy volunteers were collected. Cox proportional hazard analysis was employed to determine the prognostic value of HER2 gene copy number in tissue and cfDNA. Tissue based nomograms and time-dependent decision curve analysis were used to evaluate the practicality of HER2 copy number stratification.ResultsHER2 amplification by CNVplex demonstrated a robust concordance with FISH (concordance 89.2%). A three-tiered system of tissue and a two-tiered system of cfDNA classification were shown to be independent prognostic factors. A tissue copy number-based nomogram was fitted and further evaluation revealed a good performance in discrimination (c statistic 0.801) and calibration.ConclusionsWe first report CNVplex as a viable alternative for HER2 detection. Quantitative evaluation of HER2 presents tremendous potential for use in risk stratification. We also uncover the potential for using HER2 copy number in cfDNA as a biomarker for prognosis in a HER2 positive adjuvant setting.

Incidence of trastuzumab-induced cardiotoxicity and impact of body mass index in patients with breast cancer: Results from a Saudi tertiary cancer center.

The effect of BMI as a risk factor in trastuzumab-induced cardiotoxicity in Saudi patients with HER2-neu positive breast cancer treated with trastuzumab and anthracyclines is not fully understood. The present study retrospectively evaluated the overall incidence of cardiotoxicity and the effect of BMI as a risk factor for cardiotoxicity. A retrospective study performed between 2011 and 2015 of patients with Her2-neu positive early breast cancer who were treated with either a combination of trastuzumab and anthracycline or a combination of trastuzumab with non-anthracycline or hormonal treatment in the adjuvant settings was carried out. The incidence of cardiotoxicity and the effect of BMI, hypertension and diabetes mellitus as risk factors for cardiotoxicity were assessed. Cardiotoxicity was measured using a drop in the ejection fraction of >10 percentage points to a left ventricular ejection fraction of <50%. The present cohort included 105 patients diagnosed with stage I and II breast cancer. The mean age of the present cohort was 47.5±1.0 years (range, 25-76 years), the mean height was 153.9±14.1 cm (range, 126-170 cm), the mean body weight was 75.7±15.6 kg (range, 40-143 kg) and the mean BMI was 31.3±5.8 (range, 18-49). Cardiotoxicity was detected in 21.9% of the cohort. The BMI was calculated for 81 patients who were treated with a combination of trastuzumab and anthracycline. Cardiotoxicity was detected in 3 out of 9 patients with a BMI <25, in 9 out of 23 patients with a BMI between 25 and 29, and in 6 patients with a BMI >30. There was a significant association between cardiotoxicity and BMI (P=0.03). No significant association between age, hypertension and diabetes and cardiotoxicity was identified. In conclusion, compared with global cohorts, the present results revealed a higher incidence of cardiotoxicity among Saudi patients with HER2-neu positive early breast cancer treated with trastuzumab combinations in adjuvant settings. Increased BMI was significantly associated with cardiotoxicity.

Response-Guided Omission of Anthracycline in Patients with HER2-Positive Early Breast Cancer Treated with Neoadjuvant Taxane and Trastuzumab: 5-Year Follow-Up of Prognostic Study Using Propensity Score Matching

Background: De-escalation therapy omitting anthracycline has been generally adopted for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer in the adjuvant setting, but not in the neoadjuvant chemotherapy (NAC) setting. We investigated whether anthracycline can be omitted in HER2-positive early breast cancer patients receiving neoadjuvant taxane plus trastuzumab with clinical response. Methods: HER2-positive primary breast cancer patients treated using NAC containing trastuzumab were enrolled between September 2006 and July 2018 at Osaka Breast Clinic. The primary outcome was disease-free survival (DFS). The secondary outcome was overall survival (OS). We investigated survival with or without fluorouracil, epirubicin, and cyclophosphamide (FEC) using the log-rank test and propensity score matching (PSM). Results: In total, 142 patients were retrospectively included and median follow-up was 61 months. There was no significant difference in DFS (p = 0.93) and OS (p = 0.46) between the FEC-omitted group and the FEC-added group. The 5-year DFS was 91% and 88% and OS was 100% and 100%, respectively. After PSM, the FEC-omitted group and the FEC-added group had no significant differences in DFS (p = 0.459) and there were no death events in either group. The 5-year DFS was 90% and 88% and OS was 100% and 100%, respectively. Conclusions: Using PSM, the 5-year DFS of HER2-positive early breast cancer was not different with or without anthracycline. Response-guided omission of anthracycline may be an option for HER2-positive early breast cancer patients receiving neoadjuvant taxane and trastuzumab with good response in order to avoid overtreatment.

Practical Consensus Recommendations for Optimizing Risk versus Benefit of Chemotherapy in Patients with HR Positive Her2 Negative Early Breast Cancer in India.

Breast cancer is a public health challenge globally as well as in India. Improving outcome and cure requires appropriate biomarker testing to assign risk and plan treatment. Because it is documented that significant ethnic and geographical variations in biological and genetic features exist worldwide, such biomarkers need to be validated and approved by authorities in the region where these are intended to be used. The use of western guidelines, appropriate for the Caucasian population, can lead to inappropriate overtreatment or undertreatment in Asia and India. A virtual meeting of domain experts discussed the published literature, real-world practical experience, and results of opinion poll involving 185 oncologists treating breast cancer across 58 cities of India. They arrived at a practical consensus recommendation statement to guide community oncologists in the management of hormone positive (HR-positive) Her2-negative early breast cancer (EBC). India has a majority (about 50%) of breast cancer patients who are diagnosed in the premenopausal stage (less than 50 years of age). The only currently available predictive test for HR-positive Her2-negative EBC that has been validated in Indian patients is CanAssist Breast. If this test gives a score indicative of low risk (< 15.5), adjuvant chemotherapy will not increase the chance of metastasis-free survival and should not be given. This is applicable even during the ongoing COVID-19 pandemic.

Survival outcome and treatment tolerability for postmenopausal females with early stage hormone receptor positive breast cancer treated with different adjuvant hormonal lines (TAM vs. AI vs. switching strategy) for 5 years

Abstract Background The standard adjuvant endocrine treatment for postmenopausal female patients with hormone receptor positive early breast cancer was 5 years of tamoxifen, but recurrence and side effects restrict its usefulness. The aromatase inhibitor (anastrozole or exemestane or letrozole) was compared with tamoxifen for 5 years or started after completing 2-3 years of tamoxifen in postmenopausal female patients diagnosed with early breast cancer at "Ain Shams University Hospitals" Objective The aim of the study was to measure survival outcome and treatment tolerability for postmenopausal females with Hormone Receptor Positive early breast cancer who received adjuvant hormonal treatment with tamoxifen [TAM] only for 5 years versus those who received adjuvant hormonal treatment with tamoxifen [TAM] for 2 years switching to aromatase inhibitors [AI] in the sequential 3 years versus those who received adjuvant hormonal treatment with aromatase inhibitors [AI] solely for 5 years. Patients and methods This study included 100 postmenopausal women with early breast cancer who presented at the Clinical Oncology Department, Ain Shams University, in the interval from January 2010 until December 2015. Conclusion Similar disease free survival and overall survival were observed among the three studied groups. Switching tamoxifen to aromatase inhibitors provides better tolerability in terms of endometrial thickness when compared to 5 years of tamoxifen monotherapy. Patients who administer aromatase inhibitor included in the switching strategy experience less osteoporosis and less generalized bone pain compared to upfront aromatase inhibitor to 5 years. There was a significant improvement of disease free survival (DFS) in human epidermal growth factor receptor 2 (HER 2) negative patients receiving any adjuvant hormonal treatment line for five years in comparison to HER 2 positive patients receiving the same adjuvant hormonal treatment for five years.

Circulating and Intracellular miRNAs as Prognostic and Predictive Factors in HER2-Positive Early Breast Cancer Treated with Neoadjuvant Chemotherapy: A Review of the Literature.

Simple SummaryBreast cancer is a leading cause of female cancer-related death worldwide. Anti-HER2-targeted therapies dramatically improved prognosis for HER2-positive breast cancer patients. Despite that, growing drug resistance due to the pressure of therapy is relatively frequent. For that reason, it is necessary to find biomarkers able to predict treatment sensitivity and survival outcomes. Increasing research has shown how miRNAs, secreted by tumor cells, are strongly involved in cancer development. In this review, we will discuss the recent evidence on the predictive and prognostic value of miRNAs involved in HER2-positive early breast cancer progression.MicroRNAs (miRNA) are small noncoding RNAs that can act as both oncogene and tumor suppressors. Deregulated miRNA expression has been detected in human cancers, including breast cancer (BC). Considering their important roles in tumorigenesis, miRNAs have been investigated as potential prognostic and diagnostic biomarkers. Neoadjuvant setting is an optimal model to investigate in vivo the mechanism of treatment resistance. In the management of human epidermal growth factor receptor-2 (HER2)-positive early BC, the anti-HER2-targeted therapies have drastically changed the survival outcomes. Despite this, growing drug resistance due to the pressure of therapy is relatively frequent. In the present review, we focused on the main miRNAs involved in HER2-positive BC tumorigenesis and discussed the recent evidence on their predictive and prognostic value.

LBA11 Individual patient data meta-analysis of 5 non-inferiority RCTs of reduced duration single agent adjuvant trastuzumab in the treatment of HER2 positive early breast cancer

We planned an individual patient data (IPD) meta-analysis of non-inferiority (NI) RCTs to determine if a duration of less than the standard of 12 months (m) of adjuvant trastuzumab is non-inferior for treatment outcomes in HER-2 positive early breast cancer patients.

197P Application of neo-bioscore staging to predict the benefit of pertuzumab in HER2 positive early breast cancer

The Neo-bioscore (NB) staging system predicts the survival of patients (Pt) with early breast cancer (EBC) according to the initial clinical stage (CS), grade, estrogen receptor (ER), Her 2, and final pathological stage (PS) after neoadjuvant treatment (NeoT). Its application may be useful to assess the benefit of Pertuzumab (Pz) in the NeoT of Her 2 positive (HEBC). An NB greater than 2 is known to predict a worse prognosis.

Prognostic impact of HER2-low expression in hormone receptor positive early breast cancer

BackgroundRecent data suggest that human epidermal growth factor receptor 2 (HER2)-low breast cancer may represent a distinct entity. We aimed to compare disease characteristics and outcomes between HER2-low and HER2-0 in estrogen receptor (ER) positive, early-stage breast cancer. MethodsA single center retrospective study comprising all women with ER positive, HER2 negative early breast cancer, for whom an Oncotype DX test was performed between 2005 and 2012. Women were grouped to HER2-low (immunohistochemistry +1 or +2 and in situ hybridization not amplified) or HER2-0. Clinico-pathological features and Oncotype recurrence score (RS) were collected. Data on overall-survival (OS), disease-free survival (DFS) and distant disease-free survival (DDFS) were evaluated according to HER2 expression status. Results608 women were included, of which 304 women had HER2-0 and 304 had HER2-low disease. Lobular subtype was significantly more common in HER-0 compared to HER2-low disease (17% vs. 8%, p = 0.005). The prevalence of other clinic-pathological characteristics and long-term prognosis were comparable between both groups. For women with high genomic risk (RS > 25), HER2-low expression was associated with significantly favorable OS (HR = 0.31, 95% CI 0.11–0.78, p = 0.01), DFS (HR = 0.40, 95% CI 0.20–0.82, p = 0.01) and DDFS (HR = 0.26, 95% CI 0.11–0.63, P = 0.002) compared to women with HER2-0. For women with low genomic risk (RS ≤ 25), long-term prognosis was unrelated to HER2 expression. ConclusionThe prognostic impact of HER2-low expression in early-stage luminal disease varies across the genomic risk, with significant favorable outcomes of HER2-low expression compared to HER2-0 in women with high genomic risk.

The Cost-Effectiveness of Adjuvant Tamoxifen Treatment of Hormone Receptor–Positive Early Breast Cancer Among Premenopausal and Perimenopausal Ghanaian Women

ObjectivesMost breast cancer cases in Ghana occur in premenopausal and perimenopausal (PPM) women. This study evaluated the cost-effectiveness of tamoxifen compared with no tamoxifen for the adjuvant treatment of hormone receptor–positive (HR+) early breast cancer (EBC) among PPM Ghanaian women. MethodsA Markov model was constructed to synthesize data on the effectiveness, costs, and health benefits of tamoxifen. Effectiveness and utility data were sourced from a literature review. Resource use and healthcare costs were estimated from Ghanaian sources. The evaluation was conducted in 2017 from the perspective of the health system over a 15-year time horizon. The financial impact of funding tamoxifen on Ghana’s National Health Insurance Scheme (NHIS) was also estimated. ResultsAdjuvant tamoxifen treatment for women with HR+ EBC was more effective and more costly than no-tamoxifen therapy. The incremental benefit and costs were estimated to be 1.38 quality-adjusted life-years gained and Ghana cedis (GHC) 2338 ($520), respectively. The incremental cost-effectiveness ratio was estimated to be GHC 1694 ($376). The model was sensitive to the cost of tamoxifen and utility values. The cost of tamoxifen for the treatment of HR+ EBC represents less than 0.01% GHC 96 960 ($21 547) of the current NHIS total claims expenditure. ConclusionsTamoxifen provides additional benefits to PPM Ghanaian women with HR+ EBC and is cost-effective compared with no tamoxifen. These results support the public funding of tamoxifen under the NHIS and provide Ghanaian policy makers with vital information for future budgetary planning.

Long-term efficacy and safety of CT-P6 versus trastuzumab in patients with HER2-positive early breast cancer: final results from a randomized phase III trial

PurposeEquivalent efficacy was demonstrated for the biosimilar CT-P6 and trastuzumab following neoadjuvant therapy for patients with human epidermal growth factor receptor-2 (HER2)-positive early breast cancer. Following adjuvant treatment, efficacy and safety were comparable between treatments. We report updated safety and efficacy data after up to 3 years’ follow-up.MethodsFollowing neoadjuvant chemotherapy with CT-P6/trastuzumab, patients underwent surgery and continued receiving adjuvant CT-P6/trastuzumab. The primary endpoint (previously reported) was pathological complete response. Time-to-event analyses (disease-free survival [DFS], progression-free survival [PFS], and overall survival [OS]), study drug-related and cardiac adverse events, and immunogenicity were assessed during post-treatment follow-up.ResultsMost patients entered the follow-up period (CT-P6: 259 [95.6%]; trastuzumab: 269 [96.8%]). After a median follow-up of 38.7 (CT-P6) and 39.6 (trastuzumab) months, medians were not reached for time-to-event parameters; estimated hazard ratios (HRs) and 3-year survival rates were similar between groups. Estimated HRs (95% confidence intervals) for CT-P6 versus trastuzumab were 1.23 (0.78–1.93) for DFS, 1.31 (0.86–2.01) for PFS, and 1.10 (0.57–2.13) for OS (intention-to-treat population). Safety findings were comparable between groups for the overall study and follow-up period, including study drug-related cardiac disorders (CT-P6: 22 [8.1%] patients; trastuzumab: 24 [8.6%] patients [overall]) and decreases in left ventricular ejection fraction. Immunogenicity was similar between groups.ConclusionThe similarity of the time-to-event analyses between CT-P6 and trastuzumab supports the equivalence in terms of efficacy established for the primary endpoint. CT-P6 was well tolerated, with comparable safety and immunogenicity to trastuzumab.ClinicalTrials.gov: NCT02162667 (registered June 13, 2014)

Combined Estrogen Receptor and Progesterone Receptor Level Can Predict Survival Outcome in Human Epidermal Growth Factor Receptor 2-positive Early Breast Cancer

BackgroundIn human epidermal growth factor receptor 2 (HER2)-positive breast cancer, emerging evidence imply that clinical behaviors differ according to hormone receptor (HR) status. However, there is no conclusion about the relevance between estrogen receptor (ER) or progesterone receptor (PR) expression and clinical outcome of HER2+ breast cancer. Our study aimed to determine the influence of different ER/PR levels on survival outcome of HER2+ early breast cancer. Patients and MethodsNine hundred and nineteen early HER2+ breast cancer patients treated between 2009 and 2016 were retrospectively reviewed and HR+/HER2+ patients were further divided based on ER level (Low/L: 1%-9%; Median/M: 10%-79%; High/H: 80%-100%) and PR level (Low/L: 0%-19%; High/H: 20%-100%) according to restricted cubic spline (RCS) smoothing curve. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan–Meier method and log rank test. ResultsFour hundred and forty two HR+/HER2+ and 477 HR-/HER2+ breast cancer patients were included in our study and 73.2% received target therapy (HR+ 69.7%, HR- 76.5%). While HR+/HER2+ breast cancer showed better survival than HR-/HER2+ subtype in 5-year disease free survival (DFS, 93.0% vs. 86.8%, P < .001), no significant difference was observed between DFS in ER+/PR+ and ER+/PR- subgroup (94.4% vs. 90.4%, P = .22). However, a potential correlation was found between ER/PR levels and DFS in HR+/HER2+ (P = .074) tumors. In HR+/HER2+ breast cancer, all subgroups showed DFS improvement trend versus M-ER/L-PR. In all HER2+ patients, hazard ratio of H-ER/H-PR compared with HR- subtype was 0.10 (95%CI 0.01-0.74, P = .024) in all patients and 0.14 (95%CI, 0.02-1.02, P = .053) in patients receiving anti-HER2 therapy. ConclusionER/PR expression may become a predictor of survival benefit in HER2+ early breast cancer and a higher ER/PR level might be associated with better DFS.

Chemotherapy-induced ovarian failure in young women with early breast cancer: Prospective analysis of four randomised neoadjuvant/adjuvant breast cancer trials

BackgroundYoung women receiving chemotherapy for early breast cancer (EBC) have a high probability for ovarian failure, defined by chemotherapy-induced amenorrhea (CIA) as a surrogate. CIA is insufficiently reliable and reproducible. We analysed chemotherapy-induced ovarian failure (CIOF) by assessing hormone parameters, CIA, and antral follicle count (AFC). MethodsBlood samples of women aged ≤45 years treated with anthracycline/taxane-based chemotherapy for EBC from four neoadjuvant/adjuvant trials were collected at baseline, at the end of treatment (EOT), and at 6, 12, 18, and 24 months after EOT. Centrally assessed oestradiol (cutoff <52.2 ng/L) and follicle-stimulating hormone (cutoff >12.4IU/L) were used to define CIOF for patients with baseline premenopausal hormone levels, anti-Müllerian hormone (AMH), and AFC to assess ovarian reserve. Further analyses included CIA, regain of premenopausal hormone levels, and disease-free survival (DFS) also in subgroups. ResultsSix hundred ninety-six patients aged ≤45 years had premenopausal hormone levels at baseline. Overall, 85.1% (592/696) experienced CIOF at EOT, and 147 of 592 had further hormone measurements after EOT. Of those, 32.7% (48/147) regained premenopausal hormone levels after 6 months, 57.9% (66/114) regained premenopausal hormone levels after 12 months, 83.0% (73/88) regained premenopausal hormone levels after 18 months, and 89.2% (74/83) regained premenopausal hormone levels after 24 months. After 24 months, 72.4% (21/29) of patients without CIOF and 100% (14/14) with CIOF had low AMH levels. Four-year DFS without CIOF versus CIOF was 65.9% versus 84.6% (hazard ratio [HR] = 2.09, 95% confidence interval [CI]: 1.37–3.19; P < 0.001); in hormone receptor positive 61.8% versus 87.5% (HR = 2.69, 95% CI: 1.57–4.60; P < 0.001); in <30 years 68.3% versus 92.6% (HR = 4.87, 95% CI: 1.05–22.63; P = 0.026). ConclusionMost premenopausal women experienced CIOF after chemotherapy for EBC. After 2 years, nearly all regain premenopausal hormone levels. CIOF was associated with better DFS, especially in patients with hormone receptor–positive EBC or aged <30 years.

Real-World Clinical Outcomes of Biosimilar Trastuzumab (CT-P6) in HER2-Positive Early-Stage and Metastatic Breast Cancer.

BackgroundThe trastuzumab biosimilar CT-P6 has demonstrated equivalent efficacy and comparable safety to reference trastuzumab (RTZ) in clinical trials of human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC). Here, we present the first real-world comparison of CT-P6 versus RTZ with dual HER2-targeted therapy for the neoadjuvant and palliative first-line treatment with HER2-positive EBC and metastatic breast cancer (MBC) patients in two tertiary hospitals in Korea.MethodsWe retrospectively investigated medical records in the Severance Breast Cancer Registry in Korea. We identified patients with HER2-positive EBC (n=254) who had received neoadjuvant chemotherapy with RTZ or CT-P6, plus pertuzumab, carboplatin and docetaxel (TCHP) and untreated stage IV MBC (n=103) who had received palliative first-line treatment with RTZ or CT-P6, plus pertuzumab and docetaxel (THP) between May 2014 and December 2019. The primary endpoints were pathologic complete response (pCR) in the EBC and progression-free survival (PFS) in the MBC cohort. Overall survival (OS), overall response rate (ORR), disease control rate (DCR), and cardiac safety were secondary endpoints.ResultsA similar percentage of EBC patients achieved a pCR with CT-P6 versus RTZ (74.4% [93/125]) vs 69.8% [90/129], p=0.411). For patients with MBC, median follow-up duration was 23.0 and 41.0 months for CT-P6 and RTZ groups, respectively; median PFS did not differ significantly between two groups (13.0 vs 18.0 months, 95% confidence intervals (CIs) 0.0-26.6 vs 11.3-24.7, p=0.976). The ORR, DCR, and cardiac safety profiles did not also show significant difference efficacy outcomes between two groups.ConclusionsThese real-world data suggest that biosimilar trastuzumab CT-P6 has similar effectiveness and cardiac safety to RTZ in HER2-positive EBC and MBC patients, when administered as part of dual HER2-targeted therapy with pertuzumab plus chemotherapy in the neoadjuvant or palliative setting.

Thromboembolism (TE) and adjuvant endocrine therapy (AET) in hormone receptor positive (HR+) early breast cancer (EBC): Did the evolution of treatment change the incidence of the adverse event? A metanalysis.

e12516 Background: The AET of HR+ EBC has been changing in the recent years. Aromatase inhibitors (AI) as upfront, or in a planned switch strategy after Tamoxifen (T), have been added to the choice of T alone. An increased risk of TE is well known in the T treated patients while AIs have showed a reduced rate of TE. Recently, adding the cyclin dependent kinase 4/6 inhibitors (CDK4/6) abemaciclib to AIs, has showed a positive impact in the high risk HR+ EBC subgroups, but we are seeing an increase of the TE rate. We conducted this meta-analysis to evaluate the impact of the new AETs on the incidence of TE if compared to the standard monotherapy. Methods: We performed a meta-analysis of the randomized phase III trials comparing the experimental AETs and the endocrine standard therapy. A random-effect model to find differences in the rate of TE events between the experimental treatments and the standard therapy has been used. Results: Twelve phase III trials were included. Five trials evaluated the upfront strategy, 6 studies the switch and one the combination with a CDK4/6inhibitor (i.e. abemaciclib). Overall, the new AETs did not significantly modify or affect the rate of TE events (OR 0.708, 0.444-1.130, p = 0.148) with high heterogeneity among studies (I2 87, p &lt; 0.0001). Excluding the abemaciclib trial, the incidence of TE is reduced (OR 0.609, 0.462-0.802, p &lt; 0.0001) with a moderate heterogeneity among the studies (I2 59, p &lt; 0.006). Considering the upfront strategies with AIs, the TE events are reduced (OR 0.507, 0.394-0.651, p &lt; 0.0001) but they are not if we consider the trials in which T is used upfront before AIs (OR 0.762, 0.546-1.065, p = 0.112). Conclusions: Overall, the new treatments (AIs alone or plus CDK4/6 inhibitors) did not affect the rate in TE events. AIs as upfront strategy is the safest AETs of HR+ EBC, being associated to the lowest incidence of TE. The switch strategy increases the TE rate whereas the addition of abemaciclib to the standard AET showed to significantly increase the TE events. The results of the currently ongoing trials with the CDK4/6 inhibitors will help to obtain additional data to evaluate any differences among the different CDK4/6 inhibitors and to clarify the weight of the TE adverse events in the balance of benefit/risk of this new adjuvant strategy.

De-escalation of five years adjuvant endocrine therapy duration in patients with ER-low positive (immunohistochemical 1% to 10%) early-stage breast cancer: A propensity-matched analysis from the prospectively maintained database.

538 Background: There are limited data on endocrine therapy benefits for patients with estrogen receptor (ER)-low positive breast cancer (staining 1% to 10% of tumor nuclei by immunohistology). We aimed to compare the effect of short-term 2-3 years versus standard 5 years of adjuvant endocrine therapy on survival outcomes in patients with ER-low positive early breast cancer. Methods: We used data from the prospectively maintained Breast Surgery Database of Fudan University Shanghai Cancer Center for this propensity-matched analysis. Women with ER-low positive, operable, and unilateral early-stage invasive ductal breast cancer were enrolled in this study. Patients with advanced disease, having received neoadjuvant chemotherapy or ovarian function suppression, or with unknown duration or longer than 5 years of adjuvant endocrine therapy were excluded. Enrolled patients were divided into three groups: received no endocrine therapy; received 2-3 years of endocrine therapy; and received approximately 5 years of endocrine therapy. The primary endpoint was disease-free survival (DFS). Multivariate Cox regression analysis and propensity score matching were performed to minimize bias. Hazard ratios (HR) with 95% CIs were calculated. Results: From 2012 to 2017, 634 patients with ER-low positive breast cancer in the database met the inclusion criteria. At a median follow-up of 60 months (interquartile range, 46-74), the 5-year DFS of the whole cohort was 84.9%, with 77.6% for patients who received no endocrine therapy (N = 89), 83.7% for patients who received 2-3 years endocrine treatment (N = 185), and 87.5% for patients who received 5 years endocrine therapy (N = 360). When compared with those receiving no endocrine therapy, patients receiving 5 years treatment was associated with a significantly improved DFS (HR, 0.55; 95% CI 0.32-0.95; P = 0.03); however, there was no significant difference in DFS between patients receiving 2-3 years and 5 years endocrine therapy (HR, 0.79; 95% CI, 0.48-1.28; P = 0.33). In the multivariate Cox regression analysis of the propensity score-matched samples of 360 patients, the DFS was not significantly better for patients who received 5 years of endocrine therapy than 2-3 years treatment (HR, 0.74; 95% CI 0.41-1.34; P = 0.32). An exploratory analysis of re-biopsy of the recurrence lesions indicated more than half of relapsed disease displayed ER-negative, and less than 5% lesions were proved to be ER ≥10% positive. Conclusions: Our data did not support the necessity of 5 years duration of endocrine therapy for patients with ER-low positive breast cancer. Short-term 2-3 years duration might be an alternative option. Further translational research on identifying endocrine-sensitive cases within ER-low positive patients is needed.

Cost-effectiveness Analysis of Ado-trastuzumab Emtansine (T-DM1) for the Adjuvant Treatment of Patients With Residual Invasive HER2+ Early Breast Cancer in the United States.

Ado-trastuzumab emtansine (T-DM1) was recently approved for patients with human epidermal growth factor receptor 2 positive (HER2+) early breast cancer (eBC) with residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. Cost-effectiveness analysis was conducted to compare T-DM1 versus trastuzumab in the United States. A Markov cohort-based model tracked clinical and economic outcomes over a lifetime horizon from a US payer perspective. The model included 6 health states: invasive disease-free, nonmetastatic (locoregional) recurrence, remission, first-line and second-line metastatic BC and death. Model state transitions were based on statistical extrapolation of the head-to-head KATHERINE study and published sources. Dosing and treatment duration reflected prescribing information and trials. Costs (2019 US dollars) associated with pharmaceutical treatment (wholesale acquisition costs), health state specific care, adverse events, and end-of-life care were included. Health state utilities were obtained from KATHERINE and published literature. T-DM1 dominated trastuzumab, yielding lower lifetime costs (-$40,271), and higher life-years (2.980) and quality-adjusted life-years (2.336). Results were driven by patients receiving T-DM1 spending less time in more costly downstream health states, as these patients are less likely to experience a recurrence overall, despite having a higher likelihood of metastatic disease (distant recurrence) in the subset of patients who experience recurrence. Probabilistic sensitivity analysis indicated robust results, with 96.7% of 5000 stochastic simulations producing dominance for T-DM1. The most influential variables were related to treatment costs, off treatment utilities, and health state costs. Additional scenario analyses tested a range of model inputs and assumptions, and produced consistent results. Relative to trastuzumab, T-DM1 treatment for patients with HER2+ eBC who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment is likely to reduce the overall financial burden of cancer, while simultaneously improving patient outcomes.

Genitourinary symptoms in women with breast cancer: what do oncology health professionals think and do about them?

We aimed to improve understanding of health professional knowledge and management of genitourinary symptoms (GUS) in women with early breast cancer (EBC). A survey was sent to 872 health professionals caring for women with EBC. Questions addressed most common GUS seen, experience treating GUS, and attitudes to treatment options. 144 surveys were completed. Respondent characteristics: median age 50years; 76% female; 42% medical oncologists; 24% nurses; 20% breast surgeons; 8% radiation oncologists. Most (68%) reported prescribing endocrine therapies for EBC, 99% were aware endocrine therapies can cause GUS, and 55% reported "often" or "always" asking patients on endocrine therapy if they have GUS. Respondents thought vaginal dryness was the most bothersome symptom for their patients (66%), followed by dyspareunia (11%). 81% of respondents reported seeing women stop endocrine therapy prematurely due to GUS. Respondents reported receiving "none" (19%) or "a little" (46%) training or education in managing GUS and only 16% reported feeling "very confident" managing GUS. The proportions of respondents reporting "often" and "very often" recommending the following vaginal treatments were: lubricants (81%); moisturisers (68%); oestrogens (21%); and laser (3%). Vaginal oestrogens were considered "safe" or "probably safe" by 77% and 90% of respondents for women with hormone receptor positive and negative EBC, respectively. Despite health professionals frequently encountering GUS in women with EBC and seeing patients stop endocrine therapies prematurely, only 16% felt confident managing these symptoms. Education and training for health professionals are needed to better address this common problem.

Neratinib as extended adjuvant therapy in patients with copositive early breast cancer: German health technology assessment–driven analyses from the ExteNET study

BackgroundNeratinib is approved in the European Union for extended adjuvant treatment of human epidermal growth factor receptor 2–positive/hormone receptor–positive (copositive) early breast cancer ≤1 year of completion of prior trastuzumab-based therapy. Here, we report analyses of the hormone receptor–positive subgroup (N = 1631) from the ExteNET trial performed for the German health technology assessment (HTA). ResultsWith 2 years of median follow-up, HTA analyses revealed a significant advantage in disease-free survival (DFS) for neratinib vs. placebo (absolute/relative risk reduction: 4.1/48.2%; hazard ratio [HR] [95% confidence interval {CI}]: 0.45 [0.29; 0.69]; p = 0.0002), consistent with distant DFS (absolute/relative risk reduction: 3.1/46.3%; HR [95% CI]: 0.52 [0.32; 0.84]; p = 0.0082). The 5-year follow-up confirmed this outcome.Quality of life analyses did not show clinically relevant differences over all time points. Only at month 1, the Functional Assessment of Cancer Therapy – General total score revealed a statistically relevant difference to the disadvantage of neratinib classified as clinically relevant. The tolerability profile of neratinib was dominated by gastrointestinal events, mainly diarrhoea (all grades: 94.4%; grade III: 39.4%; no systematic antidiarrhoeal prophylaxis), nausea (all grades/grade III: 43.9/1.6%), vomiting (26.6/3.2%), abdominal pain (23.8/1.9%), fatigue (28.1/1.9%) and rash (14.3/0.4%). No cumulative or irreversible toxicities were observed. As shown in the CONTROL study and instituted via a risk management plan, diarrhoea management can reduce frequency, cumulative duration and severity of diarrhoea. ConclusionExtended adjuvant neratinib provides a clinically relevant benefit with further incremental reduction of relapse risk in the curative setting. Accordingly, the German HTA authority has granted an added benefit for this new treatment option.

52P Adjuvant endocrine therapy in HER2-positive breast cancer patients: Systematic review and meta-analysis

Approximately 50% of HER2-positive breast cancer lesions express hormone receptors. These tumors present a unique therapeutic challenge, and the optimal endocrine therapeutic approach remains controversial. We aimed to study the optimal adjuvant endocrine therapy in this setting in order to better establish the bases for clinical recommendations in HER2-positive disease. We conducted a literature search up to May 2020 in which we identified randomized controlled trials (RCTs) that investigated the efficacy of various adjuvant hormonal therapies among premenopausal and postmenopausal patients with hormone receptor (HR)-positive HER2-positive early breast cancer. Disease-free survival (DFS) was calculated with the random effect model and hazard ratios (HRs) with 95% confidence intervals (CI). Six RCTs (n=5,390 patients) were included in the final analysis. There was no significant difference in DFS between adjuvant treatment with aromatase inhibitors and tamoxifen (HR 0.99, 95% CI 0.68-1.44, P=0.96). After omitting the ALTTO trial because it did not randomize patients to hormonal therapy, no significant difference was observed between the two protocols (HR 1.06, 95% CI 0.65-1.73, P=0.81). Our study demonstrates similar DFS with tamoxifen and aromatase inhibitors as adjuvant endocrine treatment in HER2-positive HR-positive early breast cancer patients. Future larger prospective studies focusing on the various contemporary endocrine regimens are warranted to validate our findings.