Impact Of Hormone Receptor Status Research Articles

Impact of hormone receptor status and tumor subtypes of breast cancer in young BRCA carriers

Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes. This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest [disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)] were first investigated according to hormone receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer]. From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 65.5% in HER2-positive and 69.7% in luminal B-like subtype). In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.

Impact of hormone receptor status and tumor subtypes on clinical behavior and outcomes of breast cancer in young BRCA carriers.

504 Background: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer (BC). Among young patients harboring germline BRCA1or BRCA2 (BRCA) pathogenic variants (PVs), most of the tumors arising in BRCA2carriers express hormone receptors, while most BC cases in BRCA1 carriers do not; however, limited evidence exists on the impact of hormone receptor status on clinical behavior and outcomes in young patients harboring BRCA PVs. Methods: This is an international, multicenter, hospital-based, retrospective cohort study including young patients (≤40 years) diagnosed with invasive BC between January 2000 and December 2020, harboring germline PVs in BRCA genes. Our analysis investigates the impact of hormone receptor status on clinical behavior and outcomes of BC. The type and pattern of recurrence and survival outcomes (disease-free survival [DFS], BC specific survival [BCSS] and overall survival [OS]) were first investigated according to hormone receptors expression (positive vs. negative), and then according to BC subtype (luminal A-like vs. luminal B-like vs. triple-negative vs. HER2-positive BC). Results: From 78 centers worldwide, 4,709 BRCA carriers were included in this analysis, of whom 2,143 (45.5%) had hormone receptor-positive and 2,566 (54.5%) hormone receptor-negative BC. Patients with hormone receptor-positive BC were more likely to harbor BRCA2 PVs while less frequently had grade 3 tumors and nodal involvement. Median follow-up was 7.88 (IQR 4.47-12.61) years. The rate of distant recurrences was higher in patients with hormone receptor-positive BC (13.1% vs. 9.6%, p&lt;.001), while the rate of second primary BC was lower (9.1% vs. 14.7%, p&lt;.001) when compared to patients with hormone receptor-negative disease. The 8-years DFS was 65.8% in patients with hormone receptor-positive and 63.4% in those with hormone receptor-negative BC. No differences in terms of OS nor BCSS were observed. The hazard ratio of hormone receptor-positive vs. negative disease changed over time for DFS, BCSS, and OS (p&lt;.05 for interactions of hormone receptor status and survival time). Among the 4,363 patients eligible for subtypes analysis, 612 had luminal A-like, 1,038 luminal B-like, 2,373 triple-negative and 340 HER2-positive BC. Patients with Luminal A-like BC had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-years DFS: 60.8% in luminal A-like vs. 63.5% in triple-negative vs. 65.5% in HER2-positive and 69.7% in luminal B-like subtype). Conclusions: In young BRCAPVs carriers with early BC, hormone receptor status did not appear to be a positive prognostic factor. The differences in pattern of recurrence and second primary BC among hormone receptor-positive vs. negative disease warrants consideration in counseling patients on treatment, follow-up strategies and indication for risk-reducing surgery.

Abstract P4-09-03: Survival differences between HER2-zero and HER2-low-expressing breast cancer—A meta-analysis of early breast cancer patient data from 12 studies including 39831 patients

Abstract Background: HER2-low-expressing breast cancer takes up 40-50% in all breast cancer subtypes. Survival difference between HER2 low expression and HER2-zero breast cancer remains controversial. Therefore, the aim of this study was to compare the survival outcome of the two subtypes and to explore the impact of hormone receptor status. Methods:A comprehensive medical literature search was performed by PubMed, EMBASE, and the Cochrane Library through June 2022. We included observational studies reporting hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). The results of individual studies were pooled by fixed-effects models. Twelve articles with a total of 39,831 breast cancer patients were included in the meta-analysis. Results:We observed a statistically significant association between low HER2 expression levels and better breast cancer survival outcomes (OS: HR: 0.82; 95% confidence interval: 0.77, 0.88; DFS/RFS: HR: 0.88; 95% confidence interval: 0.83, 0.93). In a subgroup analysis, we found that HER2-low patients had better survival outcomes among hormone receptor-positive breast cancer patients (OS: HR: 0.85; 95% confidence interval: 0.78, 0.92; DFS/RFS: HR: 0.90; 95% confidence interval: 0.84, 0.96). Similarly, in triple-negative breast cancer patients, we also observed a positive association between HER2 low expression and better survival (OS: HR: 0.78; 95% confidence interval: 0.69, 0.87; DFS/RFS: HR: 0.86; 95% confidence interval: 0.77, 0.94). Conclusions: Our study showed that HER2 low expressing breast cancer had better survival outcomes compared to HER2 negative breast cancer in patients with early stage breast cancer, regardless of hormone receptor status. The result has a positive effect on us to further explore the clinical features, molecular characteristics and better treatment strategies of HER2-low-expressing breast cancer. Forest plot of HER2 low expression and overall survival in overall population Forest plot of HER2 low expression and disease free survival or relapse free survival in overall population Citation Format: Xiaoqi Zhang, Ciqiu Yang, Kun Wang. Survival differences between HER2-zero and HER2-low-expressing breast cancer—A meta-analysis of early breast cancer patient data from 12 studies including 39831 patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-09-03.

Impact of Hormone Receptor Status on Development of Brain Metastases from HER2+ Breast Cancer

<h3>Purpose/Objective(s)</h3> Patients with HER2+ breast cancer (BC) are at high risk of developing and dying from brain metastases (BM) compared to patients who have HER2- disease. Some studies have suggested hormone receptor (HR) positivity can delay the development of BM possibly due to endocrine therapies controlling extracranial disease. However, the impact of HR positivity on the time to development of BM in HER2+ disease is not well understood. <h3>Materials/Methods</h3> We retrospectively reviewed data on patients with BM from BC from a single academic institution from 2005–2020, during which time trastuzumab was included in the standard of care. Patients with HER2+ BC and BM were stratified into groups based on HR status, i.e., ER+ and/or PR+. Overall survival (OS) data was analyzed using the Kaplan-Meier method with differences compared by the log-rank test. HR status and time to development of BM were compared using a two-tailed Student's t-test. <h3>Results</h3> Of 363 BC patients with BM, 67 patients (18.5%) were identified as HER2+ (median age 48; range 26–80). 63 (94%) of the 67 patients received trastuzumab. 39 (58.2%) of the 67 patients had HR+ disease (ER+ and/or PR+ disease) and 28 (41.8%) had HR- disease. 30 (76.9%) of 39 patients with HR+ disease received endocrine therapy. In HR+ patients, the median time to the diagnosis of BM was 48.4 mos (SD=57.9 mos), while in patients with HR- disease the median time to the diagnosis of BM was shorter at 29.0 mos (SD=49.1 mos) (p<0.02). The median OS after initial diagnosis of BM for patients with HR+ disease was 27.6 mos, and 9.8 mos for patients with HR- disease (p<0.46). Of the 67 patients, 20 (29.9%) patients presented with one BM, 23 (34.3%) with 2–9 BM, 17 (25.4%) patients with ≥10 BM, and 7 (10.4%) with unknown number of BM. The median number of BM in HR+ patients was 2.0 (SD=2.8), and the median number of BM in HR- patients was 1.0 (SD=3.2) (p<0.43). The median diameter of the dominant BM in HR+ patients was 2.5 cm (SD=1.4 cm; range=0.05–5.4 cm), and the median diameter of the dominant BM in HR- patients was 2.1 cm (SD=1.2 cm; range=0.2–4.4 cm) (p<0.14). Brain imaging was obtained for neurological symptoms in 45 (67.2%) patients; 5 (7.5%) were asymptomatic; and 17 (22.4%) had unknown indication for imaging. 30 patients (44.8%) had extracranial metastases at the initial time of HER2+ BC diagnosis, and their median time to the development of BM was 26.4 mos (SD=25.2 mos). In contrast, 34 patients (50.7%) had no extracranial or BM at BC diagnosis and had longer median interval time to BM development at 53.8 mos (SD=67.5 mos) (p<0.002). <h3>Conclusion</h3> The majority of patients with HER2+ BM were symptomatic at time of BM diagnosis. The most salient factors associated with a decreased time interval to development of BM included HR- status and presence of extracranial metastases at the time of initial HER2+ BC diagnosis.

Abstract P4-05-02: Impact of hormone receptor status on clinicopathological characteristics and outcomes among HER2-positive metastatic breast cancer patients in the ESME database

Abstract Introduction. Evidence suggests that human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) patients have different clinical characteristics and outcomes according to the hormone receptor (HR) status. We aimed to evaluate the impact of HR status in this population extracted from a large real-world database. Methods. We performed a retrospective analysis of HER2+ MBC patients (pts) included in the real world ESME MBC database (NCT03275311) between 2008 and 2017. Descriptive statistics, the Kaplan-Meier method and Cox proportional hazards models were used to report characteristics, outcomes and prognostic factors. Results. Of 4,145 HER2+ MBC pts eligible for our analysis, 1,449 (35%) had HR-negative (HR-), while 2,696 (65%) had HR-positive (HR+) tumors. Pts with HR- tumors had metastases earlier (median 9.3 vs 28.0 mo from primary cancer), had more often de novo MBC (47.6% vs 38.1%), grade III tumors (50.9% vs 33.6%), visceral metastases (70.9% vs 60.8%) and less often bone only disease (8.4% vs 21.1%) compared to those with HR+ tumors, all p&amp;lt;0.001. Pts with HR+ MBC received less frequently an anti-HER2+ targeted therapy during first line of treatment than pts with HR- tumors (74.9% vs 90.8%, p&amp;lt;0.001). Pts with HR- MBC had significantly worse outcomes than those with HER2+/HR+ MBC, with median overall survival (OS) 42.0 mo [95% CI 38.8-45.2] vs 55.9 mo [95% CI 53.7-59.4], p&amp;lt;0.001, and median progression-free survival (PFS) 9.8 mo [95%CI 9.2-11] vs 12.2 mo [95%CI 11.5-12.9], p=0.012, respectively. The independent prognostic value of HR status was confirmed in a multivariable analysis for OS (HR- versus HR+, hazard ratio=1.25 [1.13-1.39], p&amp;lt;0.001) but not for PFS (hazard ratio=1.03 [95%CI 0.95-1.13], p=0.8) (Table 1 for OS). The multivariable analysis also included tumor grade, age at and time to MBC diagnosis, presence of visceral metastases, number of metastatic sites and performance status as prognostic factors. In the HR+ population, ER and PR statuses were not prognostic. Conclusions. These data confirm the remaining strong and independent adverse prognostic effect of negative hormone receptors among pts with HER2+ MBC treated in the past 12 years. Cox multivariable model for overall survival in patients with HER2-positive MBCCategoriesNHazard ratio95% CIp valueTumor gradeGrade I/II17711&amp;lt;0.001Grade III15741.13[1.03-1.25]NA5811.15[1.01-1.31]ER/PR statusER+/PR+14571&amp;lt;0.001ER+/PR-9711.03[0.92-1.16]ER-/PR+1021.03[0.77-1.36]ER-/PR-13961.25[1.13-1.39]Age at MBC diagnosis&amp;lt;55 years17561&amp;lt;0.001≥55 years21701.26[1.16-1.38]Time to MBC diagnosis&amp;lt;6 months16351&amp;lt;0.0016-24 months5082.53[2.22-2.89]24-60 months8721.75[1.56-1.96]≥60 months9111.19[1.06-1.35]Visceral metastasesNo14061&amp;lt;0.001Yes25201.54[1.38-1.71]No of metastatic sites&amp;lt;330911&amp;lt;0.001≥38351.65[1.48-1.84]ECOG PSPS 010101&amp;lt;0.001PS 18021.62[1.4-1.87]PS 2-43923.34[2.83-3.95]NA17222.34[2.07-2.64] Citation Format: Luc Cabel, Matthieu Carton, Veronique Dieras, Thierry Petit, Severine Guiu, Corinne Veyret, Anthony Goncalves, Lionel Uwer, Paule Augereau, Jean-Marc Ferrero, Christelle Levy, Florence Dalenc, Isabelle Desmoulins, Marie Ange Mouret-Reynier, Marc Debled, Thomas Bachelot, Jean-Christophe Eymard, Barbara Pistilli, Jean Sebastien Frenel, Michael Chevrot, Audrey Mailliez, Marcela Carausu. Impact of hormone receptor status on clinicopathological characteristics and outcomes among HER2-positive metastatic breast cancer patients in the ESME database [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-05-02.

Impact of Hormone Receptor Status on the Behaviour of HER2+ Breast Cancer.

The study aimed to evaluate differences in the overall survival of HER2+ breast cancer patients treated with regard to their hormone receptors negativity or positivity. We evaluated a cohort of patients treated with trastuzumab in the Czech Republic. The present study is a retrospective analysis of patients whose data were recorded in a nationwide non-interventional, post-authorisation database BREAST. After propensity score matching of data, the cohort included 4,532 patients. A significant difference in overall survival (OS) of the entire cohort was found between patients with and without hormone dependence. The OS was significantly higher in the group of patients with hormone receptor-positive (HR+) tumours in the following cohorts: patients treated with neoadjuvant therapy, patients with advanced disease, G2 tumours, stage III and IV and in patients with stage II and III of G2 tumours. Increased OS rates were found in several subgroups of patients with HR+/HER2+ tumours compared to those with HR-/HER2+ tumours. Better outcomes of HR+/HER2+ patients were only observed in the first four/five years of follow-up, and the differences disappeared over time.

The impact of hormone receptor status on survival and recurrence of HER2-positive breast cancers in standard adjuvant setting: A retrospective study in Tehran, Iran.

To evaluate hormone receptor status on survival and recurrence of the human epidermal growth factor receptor 2-positive breast cancer treated with Trastuzumab in the adjuvant setting. The retrospective study was conducted in 2017 at the Breast Cancer Research Centre, Tehran University of Medical Sciences, Tehran, Iran, and comprised data of women aged >20 years with stage I-III of human epidermal growth factor receptor 2-positive breast cancer who were treated with Trastuzumab from 2008 to 2017. The patients were divided into two groups. Group P had patients who were triple positive for human epidermal growth factor receptor 2, oestrogen receptor and progesterone receptor. Group N had patients positive for only human epidermal growth factor receptor 2. All patients in group P were treated with hormone therapy. Overall survival, disease-free survival, and distant metastasis rates were measured. SPSS 22 was used for data analysis. Of the 263 patients, 169(%) were in group P with a mean age of 46.86 ± 10.92 years, and 94(%) were in group N with a mean age of 48.53±12.33 years (p>0.05). There were no unfavourable predictors for overall survival and disease-free survival except for stage (p<0.05). The difference on both counts between the groups was not significant (p>0.05 each). The impact of hormone receptor positivity on survival and progression of human epidermal growth fac tor receptor 2-positive breast cancer remains an area of debate.

219P - Impact of hormone receptor status in HER2+ early breast cancer: A paradigm shift in the trastuzumab era

219P - Impact of hormone receptor status in HER2+ early breast cancer: A paradigm shift in the trastuzumab era

Impact of hormone receptor status on the efficacy of HER2-targeted treatment.

The introduction of human epidermal growth factor receptor 2 (HER2)-targeted drugs into routine clinical practice has a dramatic effect on the outlook for patients with HER2-positive breast cancer (BC). However, the association between efficacy of HER2-targeted therapy and hormone receptor (HR) status is still unclear. Here we conducted a meta-analysis of randomized controlled trials (RCTs) to address this issue in both neoadjuvant and adjuvant settings. PubMed and EMBASE were searched from inception to October 2017 for studies involving trastuzumab, lapatinib, pertuzumab, trastuzumab emtansine and neratinib. Efficacy endpoints were pathological complete response (pCR) for neoadjuvant therapy and disease-free survival (DFS) for adjuvant therapy. In neoadjuvant setting, pCR was reported in 7 trials with 2868 subjects. Hormone receptor (HR)-negative women derived substantially greater benefit from HER2-targeted agents than did HR-positive patients (odds ratio (OR), 2.34; 95% confidence interval (CI), 1.99-2.75). Additionally, the impact of HR status on pCR was independent of anti-HER2 agents. In adjuvant setting, DFS was investigated in 7 studies with 12,768 patients. HR-positive patients benefit more from anti-HER2 treatment than did HR-negative subjects (OR, 0.81; 95% CI, 0.74-0.89). Moreover, patients who did not receive any endocrine or anti-HER2 neoadjuvant treatment showed similar outcome but with a smaller effect (OR, 0.88; 95% CI, 0.78-0.99). In summary, compared with HER2-positive/HR-negative subjects, HER2-positive/HR-positive patients achieved greater benefit from HER2-targeted treatment although the efficacy from neoadjuvant therapy was relatively poor.

Impact of Hormone Receptor Status and Ki-67 Expression on Disease-Free Survival in Patients Affected by High-risk Endometrial Cancer.

The aim of this study was to evaluate the immunohistochemical (IHC) expression of Ki-67, estrogen receptors α (ERsα), and progesterone receptors (PRs) in high-risk endometrial cancer patients and to assess their prognostic impact. Immunohistochemical expression of Ki-67, ERsα, and PRs was evaluated in primary untreated endometrial cancer. The correlation among IHC staining and risk factors of recurrence such as age, Federation International of Gynecology and Obstetrics stage, grading, depth of invasion, and metastatic spread was assessed. Eighty-two patients were available for the analysis. Mean ± SD age was 65.05 ± 10.48 years. The IHC assessment revealed a lack of ERα in 46.3% and of PR in 48.7% as well as a high Ki-67 in 31.7%. Loss of ERα and PR was associated with a significant higher rate of advanced stage of disease, a higher frequency of G3 tumors, and a myometrial invasion greater than 50%. A strong Ki-67 expression correlated with a deeper myometrial invasion. Analysis of the interrelationship between receptor immunonegativity revealed a relevant association of ERα immunolocalization with PR and with a high Ki-67 expression. The present study also showed that loss of ERα (P = 0.003), advanced Federation International of Gynecology and Obstetrics stage (P < 0.001), and high Ki-67 (P = 0.004) were independent prognostic factors of a shorter disease-free survival. Importantly, loss of ERα, loss of PR, and a high Ki-67 were correlated with a higher incidence of distant recurrence. A systematic immunohistochemistry should be a key step in the therapeutic algorithm and could contribute to the identification of high-risk tumors.

Abstract P1-13-04: Impact of hormone receptor status in HER2-Positive early breast cancer in the trastuzumab era: Results of a National multi-institutional study

Abstract Background: Recent updated analysis of the HERA (HERceptin Adjuvant) trial indicate that tumor hormone receptor status (HR)remains a major determinant of outcome in HER2-positive (HER2+) early breast cancer (BC) patients, with higher rates of recurrence and death in women with HR-negative (HR-) disease, even after 11 years' median follow-up. Furthermore, data reported from the HERA trial suggest that the timing of recurrences is different, with an initial higher frequency of disease-free survival (DFS) events in patients with HR- disease than those with HR-positive disease (HR+). No evidence of a different trastuzumab efficacy according to the HR of the primary tumor was found. In this study, we examined the impact of HR on outcome in a large, multicenter, “real-world”, retrospective cohort of HER2+ early breast cancer patients Methods: HER2+ BC were retrospectively identified from a large cohort of 23,375 consecutive patients who underwent primary surgery at 17 French centers between Dec 1987 and Jan 2014. A multivariate Cox model was built including age, tumor size, SBR grade, lymphovascular invasion, lymph node involvement, hormonal receptors status, adjuvant chemotherapy, adjuvant hormone therapy, trastuzumab, radiotherapy and type of surgery. Results: A total of 1308 cases were identified, including 829 (63%) HR+ and 479 (47%) HR- patients. Median follow-up was 52 months (range 0 to 201). Compared with HR+, HR- patients had significantly smaller tumors (37 vs. 31% ≤ 10mm, p=0.027; information for multifocal tumors was not available), with higher SBR grade (58 vs. 40% grade 3, p&amp;lt;0.001) and had more lymph nodes involvement (41 vs. 32% pN+, p=0.001). HR- patients were more frequently treated by mastectomy (41 vs. 31%, p&amp;lt;0.001), received more trastuzumab (63 vs. 53%, p&amp;lt;0.001) and less radiotherapy (85 vs. 89%, p=0.020). Endocrine therapy was administered in 90% (744) of HR+ patients. No other significant difference in patient, tumor or treatment characteristics was found. HR status impacted DFS, metastasis free-survival (MFS) and BC-Specific survival (BC-SS) (hazard ratios: 0.46 [0.32-0.66]; p&amp;lt;0.001, 0.52 [0.33-0.82]; p=0.004 and 0.56 [0.34-0.90]; p=0.017, respectively), log-rank test) in overall population with higher rates of recurrence and death in women with HR- disease. In multivariate analysis, lymph node involvement and use of trastuzumab but not HR status impacted significantly DFS, MFS and BC-SS. Considering patients by treatment groups (with or without trastuzumab), HR status was not predictive of survival outcomes in the trastuzumab group, as opposed to the group without trastuzumab. Regarding the timing of recurrences, we observed an increased tendency for later relapse in patients with HR+ disease compared with HR- disease, for both DFS and MFS events. Conclusions: Our results suggest that HR status remains a major determinant of outcome in HER2+ BC, including the timing of recurrence. Yet, this prognostic impact appears to be mitigated by trastuzumab-based adjuvant treatment. Citation Format: de Nonneville A, Gonçalves A, Cohen M, Reyal F, Classe JM, Giard S, Colombo PE, Muracciole X, Chopin N, Lambaudie E, Houvenaeghel G. Impact of hormone receptor status in HER2-Positive early breast cancer in the trastuzumab era: Results of a National multi-institutional study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-13-04.

Impact of hormone receptor status and distant recurrence-free interval on survival benefits from trastuzumab in HER2-positive metastatic breast cancer

We sought to investigate the impact of hormone receptor (HR) status and distant recurrence-free interval (DRFI) on the degree of overall survival (OS) benefit from palliative trastuzumab-containing treatment in HER2-positive metastatic breast cancer (MBC). Here, we retrospectively identified 588 eligible HER2-positive patients with postoperative distant recurrence. DRFI of HR+HER2+ MBC patients (median: 30.7 months, IQR: 18.5–45.9, P < 0.001) was significant longer compared with HR−HER2+ patients. Patients were categorized into four subgroups based on HR status and palliative trastuzumab (trast+) received. The most superior outcome was observed in the HR+HER2+trast+ subgroup, with a median OS of 48.3 months. Moreover, DRFI > 24 months is an independent favourable prognostic factor for both HR−HER2+ patients (Hazard Ratio (HzR) = 0.55, 95% CI: 0.39–0.76, P < 0.001) and HR+HER2+ patients (HzR = 0.45, 95% CI: 0.32–0.64, P < 0.001). Upon further analysis of the interaction between trastuzumab and DRFI, the degree of trastuzumab benefits in HR−HER2+ MBC patients remained basically unchanged regardless of DRFI length. Unlikely, the degree in HR+HER2+ MBC patients decreased gradually along with DRFI extending, indicating that trastuzumab failed to translate into an OS benefit for late recurrent (DRFI > 5years) HR+HER2+ MBC patients.

Impact of hormone receptor status on patterns of recurrence and clinical outcomes among patients with human epidermal growth factor-2-positive breast cancer in the National Comprehensive Cancer Network: a prospective cohort study

IntroductionIn gene expression experiments, hormone receptor (HR)-positive/human epidermal growth factor-2 (HER2)-positive tumors generally cluster within the luminal B subset; whereas HR-negative/HER2-positive tumors reside in the HER2-enriched subset. We investigated whether the clinical behavior of HER2-positive tumors differs by HR status.MethodsWe evaluated 3,394 patients who presented to National Comprehensive Cancer Network (NCCN) centers with stage I to III HER2-positive breast cancer between 2000 and 2007. Tumors were grouped as HR-positive/HER2-positive (HR+/HER2+) or HR-negative/HER2-positive (HR-/HER2+). Chi-square, logistic regression and Cox hazard proportional regression were used to compare groups.ResultsMedian follow-up was four years. Patients with HR-/HER2+ tumors (n = 1,379, 41% of total) were more likely than those with HR+/HER-2+ disease (n = 2,015, 59% of total) to present with high histologic grade and higher stages (P <0.001). Recurrences were recorded for 458 patients. HR-/HER2+ patients were less likely to experience first recurrence in bone (univariate Odds Ratio (OR) = 0.53, 95% Confidence Interval (CI): 0.34 to 0.82, P = 0.005) and more likely to recur in brain (univariate OR = 1.75, 95% CI: 1.05 to 2.93, P = 0.033). A lower risk of recurrence in bone persisted after adjusting for age, stage and adjuvant trastuzumab therapy (OR = 0.53, 95% CI: 0.34 to 0.83, P = 0.005) and when first and subsequent sites of recurrence were both considered (multivariable OR = 0.55, 95% CI: 0.37 to 0.80, P = 0.002).As compared with patients with HR+/HER2+ disease, those with HR-/HER2+ disease had significantly increased hazard of early, but not late, death (hazard ratio of death zero to two years after diagnosis = 1.92, 95% CI: 1.28 to 2.86, P = 0.002, hazard ratio of death two to five years after diagnosis = 1.55, 95% CI: 1.19 to 2.00, P = 0.001; hazard ratio of death more than five years after diagnosis = 0.81, 95% CI: 0.55 to 1.19, P = 0.285, adjusting for age, race/ethnicity, stage at diagnosis, grade and year of diagnosis).ConclusionsPresenting features, patterns of recurrence and survival of HER2-positive breast cancer differed by HR status. These differences should be further explored and integrated in the design of clinical trials.

Does hormone receptor (HR) positivity affect the prognosis in breast cancers with human epidermal growth factor receptor 2 (HER2) overexpression?

e22091 Background: Biologically, there is an unclear issue about the role of HR positivity in HER2 positive breast cancer. These HER2(+)/ HR(+) pts were grouped into luminal B type apart from HER2(+)/ HR(-) pts in molecular profiling. However, from the clinical point of view, these pts have been categorized and been treated as either the only HER2(+) disease regardless of HR status or vice versa. Thus, we investigated the impact of HR status on clinical outcomes in HER2-overexpressed breast cancers. Methods: We retrospectively reviewed medical charts of HER2-positive breast cancer pts who underwent curative surgical resection from 1996 to 2001 in the Severance hospital, Korea. Demographic comparisons were performed by Chi-square tests. Tumor size, nodal stage, TNM stage, HR status, and adjuvant tamoxifen use were included in the Cox proportional hazards model. Results: Among the total 174 HER2-positive pts, HR (n=93) was positive in 53.5% (n = 93) and HR-positive tumors were more likely to be premenopausal (73% v 52%; P=0.01) and well- differentiated (grade 1or 2; 77% v 62%; P=0.04). There were no significant differences according to HR status in terms of tumor size, nodal stage, TNM stage, operation methods, and chemotherapy regimen. In these HER2-positive pts, the 5-year disease free survival (DFS) was longer in HR(+) pts than in HR(-) pts (DFS; 82.9% v 61.5%; P= 0.01). In a subset analysis, the 5-year DFS of HER2(+)/ER(+) pts without adjuvant tamoxifen (n=26) was not different from that of HER2(+)/ ER(-) pts (DFS; 57.7% v 61.5%; P= 0.32). However, the 5-year DFS of HER2(+)/ ER(+) pts with adjuvant tamoxifen was significantly prolonged compared with that of HER2(+)/ ER(-) pts (DFS; 91.5% v 61.5%; P&lt; 0.001). In a multivariate analysis of DFS, tumor size and adjuvant tamoxifen use significantly affected DFS with an adjusted hazard ratio of 2.56 (95% CI, 1.2–4.9; P= 0.01) and 6.58 (95% CI, 2.8–20.3; P&lt; 0.001), respectively. Conclusions: In an analysis of HER2-overexpressed breast cancer, the presence of HR itself did not affect the prognosis. However, most of the survival benefit seems to be driven from adjuvant tamoxifen therapy not the HR status itself. No significant financial relationships to disclose.

The impact of hormone receptor status on pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy with or without trastuzumab

533 Background: The aim of this study was to compare the extent of pathologic response in HER2-positive patients treated with standard neoadjuvant chemotherapy with or without trastuzumab according to hormone receptor (HR) status. Methods: The study included 199 patients with HER2-positive disease treated in clinical trials of neoadjuvant chemotherapy. Eighty-nine patients treated with 3- weekly paclitaxel and concurrent trastuzumab followed by 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) were compared with 110 patients treated with weekly or 3-weekly paclitaxel followed by FEC or FAC. Residual cancer burden (RCB), a measurement of residual disease (RD) from pathologic review of the primary tumor and lymph nodes, was classified as pathologic complete response (pCR), RCB-I (near-pCR, minimal RD), RCB-II (moderate RD), or RCB-III (extensive RD). RCB was compared between treatment groups according to HR status. Results: In HR-negative patients, similar pCR rates were achieved with weekly T/FAC as with 3-weekly T/FEC and trastuzumab (61% and 65%, respectively). However, in HR-positive patients, higher pCR rates were achieved with 3-weekly T/FEC and trastuzumab (47%) than with the weekly T/FAC (25%; p=0.04) or 3-weekly T/FAC (19%; p=0.01) ( Table 1 ). Near pCR (RCB-I) was slightly higher in HR-positive (26%) than in HR-negative patients treated with 3-weekly T/FEC and trastuzumab (11%; p=0.07). Conclusions: Patients with HR- negative/HER2-positive breast cancer had similar pathologic response rates from addition of trastuzumab to 3-weekly T/FEC or from weekly T/FAC chemotherapy. Patients with HR-positive/HER2-positive breast cancer obtained significant benefit from addition of trastuzumab to 3- weekly T/FEC, compared to 3-weekly T/FAC or weekly T/FAC. The combination of weekly T/FEC with trastuzumab as neoadjuvant chemotherapy should be evaluated. [Table: see text] [Table: see text]

Hormone Receptor Status Does Not Affect the Clinical Benefit of Trastuzumab Therapy for Patients with Metastatic Breast Cancer

Background Hormone receptor (HR) and HER2 signaling pathways are involved in the regulation of breast cancer proliferation. The impact of HR status on the clinical outcome of patients with HER2-overexpressing disease treated with the monoclonal antibody trastuzumab is unknown. Patients and Methods To evaluate this, we conducted a retrospective analysis of 805 patients with metastatic breast cancer enrolled in 3 clinical trials comparing trastuzumab in combination with chemotherapy versus chemotherapy alone or trastuzumab monotherapy as first-, second-, or third-line treatment. Patients whose tumor samples overexpressed HER2 by fluorescence in situ hybridization (FISH) were stratified based on HR status, and clinical outcomes were compared. Results Tumor samples from 596 of 805 patients were HER2overexpressing by FISH; 45% of these were HR-positive and 43% were HR-negative (HR status was unknown in 12%). Overall response rate (ORR) and time to progression (TTP) were significantly higher in patients treated with chemotherapy plus trastuzumab than in those treated with chemotherapy alone, irrespective of HR status. Median survival was longer for patients with HR-positive tumors receiving combination therapy compared with those with HR-negative tumors. In the trastuzumab monotherapy trials, ORR and TTP were similar for patients with HR-positive and HR-negative tumors. Median survival was longer for patients with HR-positive tumors compared with those with HR-negative tumors. Conclusion Hormone receptor status did not affect the clinical benefit of trastuzumab given as a single agent or combined with chemotherapy. The addition of trastuzumab to chemotherapy provides an improved clinical benefit compared with chemotherapy alone, regardless of HR status.

The Impact of Hormone Receptor Status on the Clinical Efficacy of the New-Generation Aromatase Inhibitors: A Review of Data From First-Line Metastatic Disease Trials in Postmenopausal Women

The Impact of Hormone Receptor Status on the Clinical Efficacy of the New-Generation Aromatase Inhibitors: A Review of Data From First-Line Metastatic Disease Trials in Postmenopausal Women

The impact of hormone receptor status on the clinical efficacy of the new-generation aromatase inhibitors: a review of data from first-line metastatic disease trials in postmenopausal women.

Hormone receptor status has long been considered important in predicting the efficacy of endocrine agents for the treatment of breast cancer. We aim to address whether hormone receptor status influences treatment outcome in postmenopausal women receiving aromatase inhibitors for advanced breast cancer. We include data from three phase III clinical trials, comparing the activity of the new-generation aromatase inhibitors, anastrozole or letrozole, with tamoxifen as a first-line treatment. For both agents, a significant relationship was observed between hormone receptor status and time to disease progression (TTP), with increased TTP seen in patients with a higher confirmed percentage of estrogen receptor (ER)- and/or progesterone receptor (PR)-positive tumors. A relationship between objective response rate (complete or partial response) or clinical benefit (complete or partial response or stabilization for > or =24 weeks) and hormone receptor status was apparent for anastrozole but not letrozole treatment. Overall these data confirm that hormone receptor status should be a strong consideration in the selection of endocrine treatment for postmenopausal women with advanced breast cancer.