Positive Hormone Receptor Status Research Articles

HLA-I and breast cancer prognosis: A systematic review and meta-analysis

BackgroundBreast cancer (BC) is a significant global health issue, accounting for 1 in 8 cancer diagnoses worldwide. HLA class I molecules are typically expressed on the cell surface, but cancer cells can develop mechanisms to evade recognition by CTLs, including the downregulation of HLA class I expression. In this context, we aimed to conduct a systematic review and meta-analysis to clarify the role of HLA class I expression in clinical outcomes for patients with BC. MethodsA comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and the Cochrane databases. Effect sizes, along with I2 and Tau2 statistics, were used to assess heterogeneity through a DerSimonian and Laird random-effects model. Statistical analyses were performed using R statistical software, version 4.2.3. ResultsAmong the 8 included studies, most of the analyzed samples consisted of ductal carcinoma cases (1588, 86.39 %), from the luminal (A or B) intrinsic subtype (1865, 69.07 %), with no lymph node metastasis (2658, 57.24 %), no HER2 overexpression (2594, 67.46 %), negative Ki67 status (1721, 71.26 %), and positive hormone receptor status (4732, 64.05 %). The analysis revealed a significant reduction in disease-free survival (HR 0.57; 95 % CI 0.34 to 0.95; p = 0.034; I2 = 84 %) in the group with low HLA-I expression. However, no significant difference was found between the groups with high and low HLA-I expression regarding overall survival (HR 0.77; 95 % CI 0.28 to 2.14; p = 0.62; I2 = 86 %). ConclusionsThis systematic review and meta-analysis demonstrated that HLA class I expression is associated with a significant improvement in disease-free survival, though no significant effect on overall survival was observed.

Physical activity levels are positively related to progression-free survival and reduced adverse events in advanced ER+ breast cancer.

Increased levels of physical activity are associated with a reduction of breast cancer mortality, especially in postmenopausal women with positive hormone receptor status. So far, previous observational case-control and cohort studies have focused on associations between overall leisure time physical activity and survival of women with breast cancer in general. In this multicenter prospective cohort study, conducted in Germany between 30th August 2012 to 29th December 2017, we investigated general physical activity in a homogenous sample of n = 1440 postmenopausal women with advanced (inoperable locally advanced or metastatic), hormone receptor-positive breast cancer receiving the same therapy (everolimus and exemestane). Self-reported physical activity was assessed using the Godin Leisure Time Exercise Questionnaire (GLTEQ) before and every 3months during treatment. Participants were then classified into "active" and "insufficiently active" to screen their activity behavior the week prior to medical treatment. In addition, changes in physical activity patterns were assessed. Adjusted Cox regression analyses were performed for the activity categories to determine hazard ratios (HR). Besides progression-free survival (PFS), adverse events (AEs), QoL, and fatigue were assessed every 3months until study termination. Compared to "insufficiently active" patients, "active" individuals indicated a significantly longer PFS (HR: 0.84 [0.74; 0.984], p = .0295). No significant differences were observed for changes of physical activity behavior. Patients who reported to be "active" at baseline revealed significantly fewer AEs compared to "insufficiently" active patients. In detail, both severe and non-severe AEs occurred less frequently in the "active" patients group. In line with that, QoL and fatigue were better in physical "active" patients compared to their insufficient active counterparts at the last post-baseline assessment. Participants who remained or become active indicated less AEs, a higher QoL, and reduced fatigue levels. Physical activity behavior prior to medical treatment might have prognostic value in patients with advanced breast cancer in terms of extending the PFS. Moreover, physical activity before and during treatment may reduce treatment-related side effects and improve patients' QoL and fatigue. EUPAS9462. Registered 30th October 2012 "retrospectively registered."

Survival outcomes of Black/African American (B/AA) patients with HER2-negative (IHC 0, 1+, 2+ and ISH-), advanced breast cancer (HER2-neg aBC) across three academic cancer centers in the United States.

129 Background: As B/AA patients are underrepresented in clinical research, data is limited on survival outcomes of B/AA patients with HER2-neg aBC. This study compared survival outcomes of these patients against those of non-B/AA patients. Methods: This was a retrospective cohort study at Huntsman Cancer Institute, H. Lee Moffitt Cancer Centre and Research Institute, and Winthrop P. Rockefeller Cancer Institute. Adult patients diagnosed with HER2-neg aBC from 2010 to 2021 were eligible. Patient data were extracted via chart review, including self-reported race from clinical records. HER2-low status was defined as immunohistochemistry (IHC) scores 1+ or 2+ and negative fluorescence in situ hybridization test; HER2-neg comprised HER2-low and IHC 0. Overall survival (OS), i.e. time until death, and progression-free survival (PFS), i.e. time until death or disease progression, were estimated using Kaplan-Meier methods with treatment start as index date and censoring at date of last follow-up or 12/31/2021, whichever earlier. Association between B/AA race and survival was evaluated using multivariable Cox regression. Results: A total of 869 patients were HER2-neg, 95 were B/AA, and 64 (67%) were HER2-low while 31 (33%) had IHC 0 disease. Compared to non-B/AA patients (85% non-Hispanic White), fewer B/AA patients had stage IV disease (38% vs 57%, p=0.001), lobular histology (3% vs 14%, p=0.001) and positive hormone receptor status (HR) (60% vs 78%, p<0.001). B/AA patients showed shorter median OS and PFS than non-B/AA patients overall and in subgroups defined by stage and HR but 95% confidence intervals (CI) overlapped (Table). Controlling for stage and HR, B/AA patients had shorter OS (Hazards ratio: 1.4, 95% CI: 1.0-1.9) but no difference in PFS (Hazards ratio: 1.2, 95% CI: 0.9-1.6). Conclusions: OS of B/AA patients with HER2-neg aBC was shorter than that of non-B/AA patients controlling for staging and HR. A sizable proportion of B/AA patients have HER2-low disease and more studies are needed to confirm if this patient population has different outcomes compared to non-B/AA. Survival outcomes of B/AA patients vs non-B/AA patients. Overall Survival (months) Progression-free Survival (months) B/AA Non-B/AA B/AA Non-B/AA n Mdn (95% CI) n Mdn (95% CI) n Mdn (95% CI) n Mdn (95% CI) Overall 95 41.4 (28.3 to 69.4) 774 56.7 (50.0 to 66.2) 95 9.9 (8.0 to 20.3) 773 16.1 (13.9 to 18.3) Staging IIIB/IIIC 60 69.4 (39.1 to NR) 339 NR (110.1 to NR) 60 10.2 (8.0 to 23.8) 339 22.5 (15.0 to 37.8) IV 35 28.1 (18.2 to 40.9) 435 39.4 (35.5 to 44.0) 35 9.6 (7.3 to 25.7) 434 13.9 (11.6 to 17.0) Hormone receptor Positive 57 41.4 (27.8 to 69.4) 609 62.0 (55.1 to 69.7) 57 8.6 (7.8 to 20.3) 609 17.1 (14.1 to 19.7) Negative 38 40.9 (23.1 to NR) 162 41.6 (24.2 to 68.3) 38 10.2 (7.7 to NR) 161 11.8 (9.3 to 17.2) B/AA – Black/African American, Mdn – median, NR – not reached.

PAM50 breast cancer subtypes and survival of patients in rural Ethiopia without adjuvant treatment: a prospective observational study

PurposeSurvival rates of breast cancer (BC) patients are particularly low in rural regions in sub-Saharan Africa (SSA) which is due to limited access to therapy. In recent years, gene expression profiling (GEP) of BC showed a strong prognostic value in patients with local tumour surgery and (neo)adjuvant treatment. The aim of this study was to evaluate the impact of intrinsic subtypes on survival of patients in rural Ethiopia without any (neo)adjuvant therapy.MethodsIn total, 113 female patients from Aira Hospital with histologically proven BC and treated only with surgery were included in this study. All samples were analysed by immunohistochemistry (IHC) for estrogen receptor, progesterone receptor, HER2 and Ki67, as well as RNA-expression analysis for PAM50 subtyping.ResultsA positive hormone receptor status was found in 69.0% of the tumours and intrinsic subtyping demonstrated Luminal B to be the most common subtype (34.5%). Follow-up data was available for 79 of 113 patients. Two-year overall survival (OS) was 57.3% and a considerably worse OS was observed in patients with Basal-like BC compared to Luminal A BC. Moreover, advanced tumours showed an increased risk of mortality.ConclusionThe OS was very low in the patient cohort that received no (neo)adjuvant treatment. Immunohistochemistry and GEP confirmed endocrine-sensitive tumours in more than half of the patients, with a large proportion of Luminal B, HER2-enriched and Basal-like tumours so that adjuvant chemotherapy should be recommended.

Clinical and Biological Significance of HER2-Low in Ductal Carcinoma In Situ of the Breast

BackgroundDuctal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer, with 5-10% of cases progressing into invasive disease. Herein, we investigated the association between HER2-low and clinico-pathological characteristics in DCIS and subsequent ipsilateral loco-regional relapse (LRR). Materials and methodsWe accessed our prospectively maintained institutional database. HER2 status was determined by immunohistochemistry and classified as null (score 0), over-expressed (3+), and low (1+ or 2+); in situ hybridization was not considered since it is not used for routine DCIS diagnostics. ResultsAmong 375 patients with DCIS, median age was 54 (27-88) years, with a primary tumor size < 2.5 cm in 63%, grade III in 33%, and positive hormone receptor status (HR) in 81% of cases; 71% underwent breast-conserving surgery, 34% received adjuvant endocrine and 39% radiotherapy. A total of 197 (52%) had tumors with low HER2 expression, which resulted significantly associated with grade I/II (P < .001), Ki67< 20% (P < .001), and HR-positive status (P < .001). HER2-low distribution varied from 19.61% and 50% in ER negative and ER-low (<10%) to 60% and 69% in ER high (50%-95%) and very high tumors (> 95%) (P < .001). After a median 39-month follow-up (IQR 16-65), cumulative incidences of LRR was 0.054. Among 17 patients with paired primary tumor and LRR, 5 had discordant HER2 status, with an even distribution of increased and decreased HER2 expression. ConclusionsLow HER2 expression in DCIS is associated with features of reduced aggressiveness. Importantly, changes in HER2 expression may occur prompting retesting in recurrent cases, in line with observations in invasive breast cancer.

Overall survival in patients with HER2-low breast cancer at a reference hospital in Mexico.

e12578 Background: Breast cancer is the most diagnosed cancer in women. The 5-year overall survival (OS) rate in early-stage disease is 97% while in advanced disease is 36%. HER2 is a growth receptor involved in cell survival and proliferation. An overexpression of this protein leads to a more aggressive behavior; however, with targeted therapies, OS has improved. Recently, a new classification has been developed for tumors previously known as HER2-negative: HER2-low; which are those with IHC 1+ or 2+/ISH negative. It is believed that in these types of tumors, the signaling pathways of the HER2-positive subtype are also activated. There are conflicting studies on the prognostic impact of this subgroup. Currently, there is availability of anti-HER2 treatment for patients in advanced stages, as described in the DESTINY-Breast04 study, which changes the treatment paradigm for this pathology. Methods: The aim of this study is to determine overall survival in patients with HER2-low breast cancer. A retrospective, analytical, observational cohort was performed. Patients diagnosed with HER2-negative/low breast cancer, treated at the UMAE Oncology Hospital of the CMN Siglo XXI, from January 2018 to December 2022, were included. OS and disease-free survival (DFS) were calculated using Kaplan-Meier curves, and the impact of HER2-low expression on OS and DFS was assessed using log-rank analysis. The prognostic analysis of the complete model was performed using a Cox proportional hazards model. Results: We included 213 patients. The median age was 57 years. Ninety-five patients were HER2-low (44.6%), and 118 were HER2-negative (55.4%). Seventy-six percent had positive hormone receptor (HR) status. Patients with HR+/HER2-negative were 84 (52.2%), and HR+/HER2-low were 77 (47.8%). Among HR-negative status, the majority were HER2-negative (65.4%). When comparing HER2-negative and HER2-low, no statistically significant differences were found, with a 48-month overall survival of 70% for HER2-negative compared to 87.1% for HER2-low (p= 0.5700). OS analysis in the HER2-low group, comparing HR+ vs. HR-, a statistically significant difference at 48 months of 98.31% vs. 49.17% (p &lt;0.0001), respectively, was found. Regarding DFS, a comparison between HR+ against HR-, it was 79.53% vs. 37.14%, respectively (p= 0.0002). The DFS analysis revealed that, among the variables studied, lymphovascular invasion (LVI) and HR+ status showed a statistically significant association with time to recurrence. Particularly, the presence of HR positivity was associated with a significant 82.6% reduction in the risk of recurrence. Conclusions: HER2 status alone (negative or low) did not offer a clear distinction in terms of OS or DFS. Nevertheless, it was observed a difference in OS and DFS outcomes favoring the HR-positive group when examining HR status among individuals with HER2-low, though this finding requires validation in a larger population.

Abstract PO5-02-07: Multifocal breast cancer: tumor biology and prognostic importance

Abstract &amp;gt;Multifocal breast cancer: tumor biology and prognostic importance Background The incidence of multifocal breast cancer (MBC) varies widely in the literature and recent reports indicate that the incidence of MBC is increasing. Several studies have shown similar tumor biology in the different foci of multifocal tumors, and it has been suggested that multifocal tumors may in fact be intramammary metastases and thus be a sign of a more aggressive cancer type than unifocal tumors. Knowledge regarding outcome and optimal treatment of MBC compared to unifocal breast cancer (UBC) is still limited. The aim of the present study was to explore if multifocal breast cancers have less favorable characteristics and prognosis compared to unifocal breast cancers. Method Patient and tumor characteristics were obtained from Breast Cancer database Sweden (BcBaSe3) including women with invasive breast cancer 2008-2019 who had undergone primary surgery. Women with distant metastases at time of diagnosis, women receiving neoadjuvant systemic therapy, and men were excluded. Overall- and breast cancer specific survival were calculated with Kaplan-Meier and Cox-regression analyses. Results A total of 71607 women met our inclusion criteria, 11961 (16.7%) with MBC and 59512 (83.3%) with UBC. Among women with MBC, 64.1% underwent mastectomy compared to 32.4% of women with UBC and 40.1% with MBC underwent complete axillary lymph node dissection compared to 23.5% of the women with UBC. MBC was associated with higher T-stage (T2 31.9% vs. 25.8% and T3 4.6% vs. 2.6%. p&amp;lt; 0.001) and higher N-stage (N+ 13.7% vs. 8.4%, P&amp;lt; 0.001), compared to UBC. MBC were more often of lobular type (18.8% vs. 12.4%, P&amp;lt; 0.001), of higher grade (grade 3 29.3% vs. 27.3%, p&amp;lt; 0.001), with positive hormone receptor status (88.4% vs. 86.7%, p&amp;lt; 0.001), and Her2 positivity (13.3% vs. 10.9%, p&amp;lt; 0.001). Adjuvant systemic treatment was more frequently administered to women with MBC, adjuvant chemotherapy (45.3% vs. 33.3%, p&amp;lt; 0.001) and endocrine treatment (82.9% vs. 75.3%, p&amp;lt; 0.001). Breast cancer specific 10- year survival was 86.4% and 88.5% for MBC and UBC respectively, hazard ratio for breast cancer death 1.19 (95 % confidence interval, 1.11- 1.28). Overall survival did not differ between the two groups (10-year survival 76.0%, p=0.35) Conclusion MBC appears to have a more aggressive tumor biology than UBC, with the exception of hormone receptor status and MBC is associated with decreased breast cancer specific survival. Further analysis of possible interactions with different treatment methods will be conducted. Citation Format: Emma Söderberg, Malin Sund, Fredrik Wärnberg, Hans Garmo, Anna-Karin Wennstig, Lars Holmberg, Greger Nilsson, Charlotta Wadsten. Multifocal breast cancer: tumor biology and prognostic importance [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-07.

Clinicopathological factors affecting response and survival in stage III breast cancer patients undergoing a dose-dense neoadjuvant regimen.

Identifying predictors of pathological complete response (pCR) and long-term outcomes after neoadjuvant treatment for breast cancer is needed to individualize treatment and patient monitoring. This study aimed to investigate clinicopathological factors affecting pCR and long-term outcomes in stage III breast cancer patients receiving a dose-dense neoadjuvant regimen. This is a retrospective study including patients with stage III breast cancer who received neoadjuvant chemotherapy consisting of doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m², followed by paclitaxel 175 mg/m² every two weeks at Vietnam National Cancer Hospital and Hanoi Oncology Hospital between January 2015 and December 2022. Logistic and Cox regression were used to investigate the association between clinicopathological factors and pCR and long-term outcomes, respectively. A total of 211 patients were included in the study. Univariate analysis found an association of pCR with clinical tumor (cT) stage, grade, hormone receptor status, HER2, Ki67, and St. Gallen classification. Multivariate analysis identified several predictors of pCR: cT stage (cT3/T4 vs cT1/T2: OR: 0.3; p = 0.01); grade (grade 3 vs grade 1-2: OR: 1.6; p = 0.035); and hormone receptor status (nega-tive vs. positive: OR: 2.9; p = 0.011). Two independent prognostic factors for event-free survival (EFS) were identified: hormone receptor status (negative vs. positive: HR: 2.1; p = 0.044) and pCR (No pCR vs. pCR: HR: 3.0; p = 0.018). Hormone receptor status was also the only independent prognostic factor for overall survival (OS) (negative vs. positive: HR: 2.6; p=0.039). Low cT stage, grade 3, and hormone receptor-negative status were independent predictors of pCR. Hormone receptor-positive status and pCR were independent prognostic factors for better EFS, while hormone receptor-positive status was the only independent prognostic factor for better OS.

Clinicopathologic Features and Prognoses of Male Patients With Breast Cancer.

Breast cancer is rare in men and is managed using strategies similar to those for breast cancer in women. This study retrospectively analyzed the clinicopathological features, treatment, and survival of male breast cancer (MBC). A total of 66 patients with MBC admitted into Xijing Hospital from August 2006 to March 2024 were reviewed. Data were collected from patients' hospital records and breast cancer database of Xijing Hospital. The incidence of MBC tended to increase from 2018, with affected individuals being older than those with female breast cancer (FBC). The most common histological type of MBC was invasive carcinoma, with positive hormone receptor status. A total of 62 (93.9%) patients with MBC underwent modified radical mastectomy. Chemotherapy was administered to 39 (59.1%) patients, while endocrine therapy was received by 14 patients (21.2%) and radiotherapy by nine patients (13.6%). Survival analysis indicated that the median overall survival (OS) of patients with MBC was 46.7 months (0.9-184.8 months). As of the latest data, 58 patients (87.9%) with MBC are alive. Factors significantly associated with survival included age (χ2 = 3.856, p = .050), estrogen receptor (χ2 = 10.427, p = .005), molecular types (χ2 = 10.641, p = .031), P63 (χ2 = 2.631, p < .001), and endocrine therapy (χ2 = 31.167, p < .001). These findings provide valuable insights into MBC within the Chinese population and serve as a reference for the standard treatment of MBC.

Skeletne metastaze karcinoma dojke - uticaj hormonskih i receptora humanog epidermalnog faktora rasta 2

Breast cancer is the leading cause of cancer-related deaths among women worldwide. While significant progress has been made in the prophylaxis, diagnosis, and management of breast cancer, around 90% of deaths occur due to metastatic disease, which is still incurable. The bone has been identified as one of the predominant metastatic sites, accounting for around 80% of patients with metastatic breast cancer. The paper aims to summarize the hallmarks of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) influence on breast cancer bone metastases development and their further biological and clinical behavior. Various clinicopathological characteristics have been identified as risk factors for the development of metastases. In particular, the status of ER, PR and HER2 is crucial for making clinical decisions as an important tool for predicting the spread of breast cancer and choosing a therapeutic protocol. Patients with any hormone receptor-positive status, particularly those with ER+, PR+/HER2-, are more likely to develop bone-only-metastatic (BOM), whereas those with hormone receptor-negative status, especially those with so-called triple-negative (HR-/HER2-) or HER2+ breast cancer, have a predilection for visceral metastases. The paper highlights that while bone metastases of breast cancer are much less investigated than primary tumors, more studies are needed to understand the complex, multi-step process involved in the development and behavior of bone metastases.

Evolution and prognostic significance of HER-2 conversion from primary to residual disease in HER-2 negative patients with breast cancer after neoadjuvant chemotherapy.

This study aimed to analyze HER-2 zero or HER-2 low conversion in HER-2 negative patients after neoadjuvant chemotherapy (NAC) and evaluate its prognostic significance. HER-2 negative patients with breast cancer with residual disease after NAC and paired pre- and post-therapeutic HER-2 testing results were analyzed retrospectively. HER-2 low, defined as immunohistochemistry (IHC) scores of 1+ or 2+/in situ hybridization (ISH), were not amplified. HER-2 zero is defined as an IHC score of 0. A total of 571 patients were enrolled, including primary HER-2 zero (n=201, 35.2%) and HER-2 low (n=370, 64.8%). The overall HER-2 change rate was 32.4%. Multivariable logistic regression showed that patients with hormone receptor-positive status before NAC was significantly associated with the conversion of HER-2 zero to low (OR=3.436, P < 0.0001). The median follow-up time was 50.0 months. In patients who are primary HER-2 zero, HER-2 zero to low was significantly associated with better disease-free survival (DFS) than constant HER-2 zero (HR=0.49, P=0.01) after adjustment (4-year DFS 80.1% vs 55.7%, Log-rank P=0.033). Subgroup analysis revealed that among patients who are primary HER-2 zero with hormone receptor-positive, HER-2 zero to low had a significantly better DFS than constant HER-2 zero (Log-rank P=0.037). In contrast, patients with hormone receptor-negative status did not. In conclusion, almost one-third of patients who are HER-2 negative underwent HER-2 zero or HER-2 low conversion after NAC. HER-2 zero to low conversion was associated with better DFS in patients who are HER-2 zero. These results provide a valuable reference for the potential application of anti-HER-2 ADC in an adjuvant setting for patients with residual disease after NAC.

Breast Cancer Tissue Explants: An Approach to Develop Personalized Therapy in Public Health Services.

Breast cancer is one of the main causes of death worldwide. Lately, there is great interest in developing methods that assess individual sensitivity and/or resistance of tumors to antineoplastics to provide personalized therapy for patients. In this study we used organotypic culture of human breast tumor slices to predict the experimental effect of antineoplastics on the viability of tumoral tissue. Samples of breast tumor were taken from 27 patients with clinically advanced breast cancer; slices were obtained and incubated separately for 48 h with paclitaxel, docetaxel, epirubicin, 5-fluorouracil, cyclophosphamide, and cell culture media (control). We determined an experimental tumor sensitivity/resistance (S/R) profile by evaluating tissue viability using the Alamar Blue® metabolic test, and by structural viability (histopathological analyses, necrosis, and inflammation). These parameters were related to immunohistochemical expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The predominant histological type found was infiltrating ductal carcinoma (85.2%), followed by lobular carcinoma (7.4%) and mixed carcinoma (7.4%). Experimental drug resistance was related to positive hormone receptor status in 83% of samples treated with cyclophosphamide (p = 0.027). Results suggest that the tumor S/R profile can help to predict personalized therapy or optimize chemotherapeutic treatments in breast cancer.

Prognostic factors in hormone receptor positive oligometastatic breast cancer.

1058 Background: Some recommend curative treatment for oligometastatic breast cancer (OMBC). To date, no randomized clinical trial has demonstrated the benefits of such a strategy. We present the largest retrospective series of patients treated consecutively for ER and/or PR positive (HR+) OMBC in a single institution. The objective was to describe the clinical and biological characteristics and prognostic factors of HR+ OMBC. Methods: We retrospectively reviewed all patients treated consecutively from 2014 to 2018 at our institution for synchronous or metachronous metastatic breast cancer (MBC). HR+ OMBC was defined as MBC with up to five metastases at diagnosis, positive hormone receptor status, and no other inclusion criteria. Clinical and biological characteristics, treatment modalities - intent-to-cure vs palliative - and outcomes were recorded. Progression-free survival (PFS) and overall survival (OS) were calculated. Log rank test and Cox regression models were used for survival analyses including time-dependent variable. Results: Of 998 patients treated for MBC within our institution between 2014 and 2018, 11.3% (N=113/998) met inclusion criteria. 62.5% of them had SBR grade I/II HR+ OMBC and 80.5% had HR+/HER2- OMBC. 89.3% patients had only one organ involved. None had more than two; 89.3% patients had 1-3 metastases at diagnosis. Among these 113 patients, 63.7% had bone metastases, 54.9% had bone only metastases, 19.5% had visceral metastases, 17.7% had lymph node metastases, 7.1% had brain metastases, and 3.5% had other metastases. Forty-one patients (36.3%) were treated in a curative intent with systemic treatment plus ablative focal treatment of primary tumor – or local relapse – and all distant metastases. Median follow up was 67.2 months (95%CI= [63.1-75.4]). For the entire series, five-year PFS and OS were respectively 35.2% (95%CI= [25.6-44.6]) and 67.0% (95%CI= [56.7-75.3]) respectively. In univariable analysis, liver metastases was associated with worse OS (HR=3.13, 95%CI=[1.43-6.87], p=0.003). In multivariable analysis, HER2 positive status (HR=0.43, 95%CI= [0.21-0.90], p=0.024), bone only metastases (HR=0.46, 95%CI= [0.27-0.78], p=0.004), and intent-to-cure treatment (HR=0.53, 95%CI= [0.30-0.93], p=0.027) were significantly associated with longer PFS. In multivariate analysis, only intent-to-cure strategy was associated with better OS (HR=0.24, 95%CI= [0.09-0.60], p=0.002). Conclusions: This is the largest retrospective series of patients treated consecutively for HR+ OMBC to date. 71.5 % of OMBC and 11.3 % of all MBC are HR+ OMBC. Most had only one invaded organ and 1-3 metastases. Among our cohort, intent-to-cure treatment improve drastically HR+ OMBC PFS and OS. A multimodal intent-to-cure strategy should be routinely discussed for patients with HR+ metastatic breast cancer with one to five metastases at diagnosis.

Abstract P4-03-34: Treatment Patterns and Associated Outcomes Among Patients with HER2+ Metastatic Breast Cancer in the United States

Abstract Background Historically, standard-of-care treatments for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC) have been pertuzumab and trastuzumab combined with a chemotherapeutic agent in first line (1L), and trastuzumab emtansine (T-DM1) in the second line (2L). However, two new treatments have recently been approved for patients who previously received HER2-targeted therapy; fam-trastuzumab deruxtecan-nxki [Enhertu®] and tucatinib [Tukysa] (in triplet combination) in 2019 and 2020, respectively. The goal of this study was to characterize treatment patterns of patients with HER2+ mBC from receipt of first line therapy and subsequent treatments received in real world community oncology practices. Methods Adults diagnosed with HER2+ mBC from January 2013 – January 2021 were selected from the Flatiron Health electronic health record–derived database; a US-wide database curated from community clinics that comprises de-identified patient-level structured and unstructured data. Patients were followed from index date (start of 1L therapy) to death or last activity date. Descriptive statistics reported baseline patient characteristics and treatment patterns. Time to treatment discontinuation (TTD), real-world progression-free survival (rwPFS), and real-world overall survival (rwOS) were estimated using the Kaplan-Meier method. Results A total of 2,074 mBC HER2+ patients with at least 1 line of therapy were included during the study time period. Median follow-up time was 26.0 months (Interquartile range [IQR]: 12.6-44.7). Patients were mostly white (62.7%), median age 61 years (IQR:24-84), 43.0% were stage IV at initial breast cancer diagnosis, and 62.8% had positive hormone receptor (HR) status. Of the 2,074 patients in our study population, 1,159 (55.8%) received 2L therapy, and 584 (28.2%) received a 3L therapy. In terms of 1L therapy, 1,607 (77.5%) received a trastuzumab-based (T-based) regimen, 205 (9.9%) received chemotherapy only, and 153 (7.4%) received a T-DM1 based therapy. The most common regimens across 1L included pertuzumab+trastuzumab+taxane (THP) (38.9%), THP + a platinum agent (7.5%), and T-DM1 (6.1%). From start of 1L, overall median TTD was 10.8 months (95% confidence interval [CI]: 10.1-11.5), median rwPFS was 11.5 months (95% CI: 10.8-12.3), and median rwOS was 40.3 months (95% CI: 37.8-43.4). Among the 1,607 patients who received any T-based regimen in 1L, 496 (30.9%) received T-DM1, 175 (10.9%) received a T-based regimen again, 78 (4.9%) received any other HER2-based regimen, 59 (3.7%) received hormonal therapy alone and 33 (2.1%) received chemotherapy. The most common regimens across 2L (n=1,159) were T-DM1 monotherapy (35.7%), THP (11.2%), and T-DM1+hormone therapy (8.0%). From start of 2L, overall median TTD was 8.3 months (95% CI: 7.6-9.0), median rwPFS was 7.4 months (95% CI: 6.8-8.1), and median rwOS was 27 months (95% CI: 25.9-30.0). Conclusions Variability, which may impact outcomes, is observed in treatment approaches for HER2+ mBC. Additionally, more than half the patients on 1L treatment progressed within a year of initiating treatment, highlighting a remaining need for effective therapies that limit progression and maintain clinical benefit in 1L. Citation Format: Clara Lam, Della Varghese, Beth L. Nordstrom, Brian Murphy, Jenna Collins, Sandhya Mehta. Treatment Patterns and Associated Outcomes Among Patients with HER2+ Metastatic Breast Cancer in the United States [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 P4-03-34.

Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival.

A polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer. Women with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS313 (continuous, per standard deviation) with overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment. The PRS313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS313 was associated with lower grade, hormone receptor-positive status, and smaller tumor size. In MINDACT, PRS313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent. An increased PRS313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS313 as increasing PRS313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.

Tumor biomarkers and efficacy in patients treated with trastuzumab emtansine + pertuzumab versus standard of care in HER2-positive early breast cancer: an open-label, phase III study (KRISTINE)

BackgroundKRISTINE is an open-label, phase III study of trastuzumab emtansine + pertuzumab (T-DM1 + P) versus docetaxel + carboplatin + trastuzumab + pertuzumab (TCH + P) in patients with HER2-positive, stage II–III breast cancer. We investigated the association of biomarkers with clinical outcomes in KRISTINE.MethodsPatients were randomized to receive neoadjuvant T-DM1 + P or TCH + P and assessed for pathologic complete response (pCR; ypT0/is, ypN0). HER2 status (per central assessment), hormone receptor status, PIK3CA mutation status, HER2/HER3 mRNA levels, tumor-infiltrating lymphocyte levels, PD-L1 status, and NanoString data were analyzed. pCR rates by treatment arm were compared across biomarker subgroups. Analyses were descriptive.ResultsBiomarker analyses included data from all 444 patients (T-DM1 + P, n = 223; TCH + P, n = 221) enrolled in KRISTINE. Biomarker distribution was balanced across treatment arms. All subgroups with higher HER2 amplification/expression and immune marker levels showed numerically higher pCR rates in both arms. Mutated versus non-mutated PIK3CA tumors were associated with numerically lower pCR rates in the T-DM1 + P arm but not in the TCH + P arm. In a multivariate analysis, Prediction Analysis of Microarray with the 50-gene classifier (PAM50) HER2-enriched subtype, HER2 gene ratio ≥ 4, and PD-L1-positive status positively influenced the pCR rate. Biomarkers associated with lower pCR rates (e.g., low HER2 levels, positive hormone receptor status, mutated PIK3CA) were more likely to co-occur. Dynamic on-treatment biomarker changes were observed. Differences in the treatment effects for T-DM1 + P versus TCH + P were similar to those observed in the intent-to-treat population for the majority of the biomarker subgroups.ConclusionsAlthough our biomarker analysis did not identify a subgroup of patients that benefited from neoadjuvant T-DM1 + P versus TCH + P, the data revealed that patients with higher HER2 amplification/expression and immune marker levels had improved response irrespective of treatment arm. These analyses confirm the role of HER2 tumor biology and the immune microenvironment in influencing pCR in the neoadjuvant setting and reaffirm the molecular diversity of HER2-positive breast cancer.Trial Registration: ClinicalTrials.gov NCT02131064. Registered 06 May 2014.

Efficacy and Safety of Pyrotinib in Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: A Multicenter, Retrospective, Real-World Study.

PurposePyrotinib, a novel human epidermal growth factor receptor 2 (HER2)-targeted tyrosine kinase inhibitor (TKI), has led to remarkable survival outcomes in HER2-positive advanced breast cancer (ABC) in clinical trials and was approved for second-line standards of treatment for HER2+ ABC in China. However, the clinical trials could not fully reflect reality of clinical practice, and predictive factors were still lacking. This study aimed to assess the actual efficacy and safety of pyrotinib in HER2+ ABC in real-world setting.Patients and MethodsIn this multicenter, retrospective, observational real-world study, we analyzed 171 patients with HER2+ ABC, who received pyrotinib-based treatment from November 2017 to November 2020. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety.ResultsUp to November 30, 2021, the median PFS (mPFS) was 12.0 months for all patients. One hundred and sixty-two patients (94.7%) with measurable lesions had been included in efficacy assessment. The ORR and CBR were 45.1% and 81.5%, respectively. A significantly longer PFS was reported in patients who received pyrotinib as first-line treatment, had the ECOG-PS of 0–1, as well as those who were lapatinib-naive. In addition, multivariable analysis indicated that ECOG-PS of 2–4, positive hormone receptor (HR) status, and presence of visceral metastasis were independent negative predictors of PFS. As far as we know, this study first reported the survival outcome of pyrotinib cross-line treatment, with a mPFS of 5.0 months. All grades of adverse events (AEs) occurred in 171 patients (100%), and the most common AE was diarrhea (86.5%).ConclusionThis study further demonstrated the outstanding efficacy and safety of pyrotinib and reported the potential predictors of survival in HER2+ ABC.

Comparative review of pharmacological therapies in individuals with HER2-positive advanced breast cancer with focus on hormone receptor subgroups.

Breast cancer is the fifth leading cause of cancer-related deaths worldwide. The randomized controlled trials (RCTs) of targeted therapies in human epidermal receptor 2 (HER2)–positive advanced breast cancer (ABC) have provided an evidence base for regulatory and reimbursement agencies to appraise the use of cancer therapies in clinical practice. However, a subset of these patients harbor additional biomarkers, for example, a positive hormone receptor status that may be more amenable to therapy and improve overall survival (OS). This review seeks to explore the reporting of evidence for treatment effects by the hormone receptor status using the RCT evidence of targeted therapies for HER2-positive ABC patients. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed to identify published RCTs. Extracted data were synthesized using network meta-analysis to obtain the relative effects of HER2-positive-targeted therapies. We identified a gap in the reporting of the effectiveness of therapies by the hormone receptor status as only 15 out of 42 identified RCTs reported hormone receptor subgroup analyses; the majority of which reported progression-free survival but not OS or the overall response rate. In conclusion, we recommend that future trials in ABC should report the effect of cancer therapies in hormone receptor subgroups for all outcomes.

Oncologic Outcome of 1000 Postmastectomy Breast Reconstructions with Fat Transfer: A Single-Center, Matched Case-Control Study.

Autologous fat transfer has an important role in breast reconstructive surgery. Nevertheless, some concerns remain with regard to its oncologic safety. The authors present a single-center, case-matching study analyzing the impact of autologous fat transfer in the cumulative incidence of local recurrences. From a prospectively maintained database, the authors identified 902 patients who underwent 1025 breast reconstructions from 2005 to 2017. Data regarding demographics, tumor characteristics, surgery details, and follow-up were collected. Exclusion criteria were patients with distant metastases at diagnosis, recurrent tumor, or incomplete data regarding primary tumor; and patients who underwent prophylactic mastectomies and breast-conserving operations. Statistical analysis was conducted to evaluate the impact of the variables on the incidence of local recurrence. A value of p < 0.05 was considered statistically significant. After 1: n case-matching, we selected 919 breasts, of which 425 patients (46.2 percent) received at least one autologous fat transfer session versus 494 control cases (53.8 percent). Local recurrences had an overall rate of 6.8 percent, and we found local recurrences in 14 autologous fat transfer cases (3.0 percent) and 54 controls (9.6 percent). Statistical analysis showed that autologous fat transfer did not increase the risk of local recurrences (hazard ratio, 0.337; CI, 0.173 to 0.658; p = 0.00007). Multivariate analysis identified invasive ductal carcinoma subtype and lymph node metastases to have an increased risk of local recurrences (hazard ratio >1). Conversely, positive hormonal receptor status was associated with a reduced risk of events (hazard ratio <1). Autologous fat transfer was not associated with a higher probability of locoregional recurrence in patients undergoing breast reconstruction; therefore, it can be safely used for total breast reconstruction or aesthetic refinements. Risk, II.

24. IMPACT OF AUTOLOGOUS FAT TRANSFER ON CUMULATIVE INCIDENCE OF LOCAL RECURRENCE IN 1,000 POST-ONCOLOGIC BREAST RECONSTRUCTION:A SINGLE CENTER MATCHED CASE-CONTROL STUDY

PURPOSE: Autologous fat transfer (AFT) has an important role in breast reconstructive surgery. Nevertheless, Some concerns remain with regards to its oncological safety. We present a single center case-matching study analysing the impact of AFT in cumulative incidence of local recurrences (LR). METHODS: From a prospectively maintained database, we identified 902 patients who underwent 1025 breast reconstructions from 2005 to 2017. Data regarding demographics, tumor characteristics, surgery details and follow-up were collected. Exclusion criteria were patients with distant metastases at diagnosis, recurrent tumor or incomplete data regarding primary tumor, patients who underwent prophylactic mastectomies and breast-conserving surgeries. Statistical analysis was done to evaluate the impact of the variables on the incidence of LR. A p-value < 0.05 was considered statistically significant. RESULTS: After 1:n case-matching, we selected 919 breasts, out of which 425 (46.2%) patients received at least one AFT session vs 494 (53.8%) control cases. LR had an overall rate of 6.8% and we found LR in 14 (3.0%) AFT cases and 54 (9.6%) controls. Statistical analysis showed that AFT did not increase risk of LR: HR 0.337 (CI 0.173-0.658), p=0.00007. Multivariate analysis identified IDC subtype and lymph node metastases to have an increased risk of local recurrences (HR > 1). Conversely, positive hormonal receptor status was associated with a reduced risk of events (HR < 1) CONCLUSION: AFT was not associated with a higher probability of locoregional recurrence in patients undergoing breast reconstruction therefore it can be safely used for total breast reconstruction or aesthetic refinements.