scholarly journals Inflammatory Potential of the Diet and Risk of Breast Cancer in the European Investigation Into Cancer and Nutrition (EPIC) Study

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 264-264
Author(s):  
Carlota Castro-Espin ◽  
Antonio Agudo ◽  
Catalina Bonet ◽  
Elisabete Weiderpass ◽  
Elio Riboli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Menopausal Status ◽  
Premenopausal Women ◽  
Potential Effect ◽  
Funding Sources ◽  
Inflammatory Score ◽  
Increased Risk ◽  
Incident Breast Cancer ◽  
Prospective Investigation

Abstract Objectives We aimed to evaluate the association between the inflammatory potential of the diet and the risk of breast cancer overall, by tumour subtypes and according to menopausal status. Methods A total of 318,686 women from the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for 14 years, among whom 13,246 incident breast cancer cases were identified. Dietary inflammatory potential was characterized by an inflammatory score of the diet (ISD). Multivariable Cox regression models were used to assess the potential effect of the ISD on the risk of overall breast cancer and by tumour subtypes by means of the hazard ratio (HR) and 95% confidence interval (95% CI). Results ISD was positively associated with breast cancer risk. Adjusted for relevant confounders, each increase of one standard deviation (1-SD) of the score increased by 4% the risk of breast cancer (HR 1.04; 95% CI: 1.01–1.07). Women in the highest quintile of the ISD (indicating most pro-inflammatory diet) had a 12% increase in risk compared with those in the lowest quintile (HR 1.12; 95% CI: 1.04–1.21) with a significant trend. The association was more pronounced among premenopausal women, with increased risk of 8% for 1-SD increase of the score (HR 1.08; 95% CI: 1.01–1.14). The pattern of the association was quite homogeneous by tumour subtypes based on hormone receptor status. There were no significant interactions  between ISD and body mass index, physical activity or alcohol consumption. Conclusions Women consuming more pro-inflammatory diets as measured by ISD are at increased risk for breast cancer, especially premenopausal women. Funding Sources

scholarly journals Inflammatory Potential of the Diet and Risk of Breast Cancer in the European Investigation Into Cancer and Nutrition (EPIC) Study

2021 ◽  
Author(s):  
Carlota Castro-Espin ◽  
Antonio Agudo ◽  
Catalina Bonet ◽  
Verena Katzke ◽  
Renée Turzanski-Fortner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Physical Activity ◽  
Cox Regression ◽  
Menopausal Status ◽  
Premenopausal Women ◽  
Underlying Mechanism ◽  
Potential Effect ◽  
Inflammatory Score ◽  
Hazard Ratios ◽  
Increased Risk

Abstract The role of chronic inflammation on breast cancer (BC) risk remains unclear beyond as an underlying mechanism of obesity and physical activity. We aimed to evaluate the association between the inflammatory potential of the diet and risk of BC overall, according to menopausal status and tumour subtypes. Within the European Prospective Investigation into Cancer and Nutrition cohort, 318,686 women were followed for 14 years, among whom 13,246 incident BC cases were identified. The inflammatory potential of the diet was characterized by an inflammatory score of the diet (ISD). Multivariable Cox regression models were used to assess the potential effect of the ISD on BC risk by means of hazard ratios (HR) and 95% confidence intervals (CI). ISD was positively associated with BC risk. Each increase of one standard deviation (1-Sd) of the score increased by 4% the risk of BC (HR=1.04; 95% CI: 1.01-1.07). Women in the highest quintile of the ISD (indicating most pro-inflammatory diet) had a 12% increase in risk compared with those in the lowest quintile (HR=1.12; 95% CI: 1.04-1.21) with a significant trend. The association was strongest among premenopausal women, with an 8% increased risk for 1-Sd increase in the score (HR=1.08; 95% CI: 1.01-1.14). The pattern of the association was quite homogeneous by BC subtypes based on hormone receptor status. There were no significant interactions between ISD and body mass index, physical activity or alcohol consumption. Women consuming more pro-inflammatory diets as measured by ISD are at increased risk for BC, especially premenopausal women.

scholarly journals Dietary Constituents: Relationship with Breast Cancer Prognostic (MCC-SPAIN Follow-Up)

2020 ◽  
Vol 18 (1) ◽  
pp. 84
Author(s):  
Trinidad Dierssen-Sotos ◽  
Inés Gómez-Acebo ◽  
Nuria Gutiérrez-Ruiz ◽  
Nuria Aragonés ◽  
Pilar Amiano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protective Effect ◽  
Dietary Habits ◽  
Cox Regression ◽  
Menopausal Status ◽  
Premenopausal Women ◽  
Normal Weight ◽  
High Intake ◽  
The Relationship

The aim of this study was to characterize the relationship between the intake of the major nutrients and prognosis in breast cancer. A cohort based on 1350 women with invasive (stage I-IV) breast cancer (BC) was followed up. Information about their dietary habits before diagnosis was collected using a semi-quantitative Food Frequency Questionnaire. Participants without FFQ or with implausible energy intake were excluded. The total amount consumed of each nutrient (Kcal/day) was divided into tertiles, considering as “high intakes” those above third tertile. The main effect studied was overall survival. Cox regression was used to assess the association between death and nutrient intake. During a median follow-up of 6.5 years, 171 deaths were observed. None of the nutrients analysed was associated with mortality in the whole sample. However, in normal-weight women (BMI 18.5–25 kg/m2) a high intake of carbohydrates (≥809 Kcal/day), specifically monosaccharides (≥468 Kcal/day), worsened prognostic compared to lowest (≤352 Kcal/day). Hazard Ratios (HRs) for increasing tertiles of intake were HR:2.22 95% CI (1.04 to 4.72) and HR:2.59 95% CI (1.04 to 6.48), respectively (p trend = 0.04)). Conversely, high intakes of polyunsaturated fats (≥135 Kcal/day) improved global survival (HR: 0.39 95% CI (0.15 to 1.02) p-trend = 0.05) compared to the lowest (≤92.8 kcal/day). In addition, a protective effect was found substituting 100 kcal of carbohydrates with 100 kcal of fats in normal-weight women (HR: 0.76 95% CI (0.59 to 0.98)). Likewise, in premenopausal women a high intake of fats (≥811 Kcal/day) showed a protective effect (HR:0.20 95% CI (0.04 to 0.98) p trend = 0.06). Finally, in Estrogen Receptors (ER) negative tumors, we found a protective effect of high intake of animal proteins (≥238 Kcal/day, HR: 0.24 95% CI (0.06 to 0.98). According to our results, menopausal status, BMI and ER status could play a role in the relationship between diet and BC survival and must be taken into account when studying the influence of different nutrients.

scholarly journals Interaction of H3K27me3 and Glutaminase 1 Expression on Breast Cancer Prognosis by Menopausal Status: a Cohort Study

2021 ◽  
Author(s):  
Meng Zhou ◽  
Qianxin Chen ◽  
Yuanzhong Yang ◽  
Zhuozhi Liang ◽  
Yuelin Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Menopausal Status ◽  
Premenopausal Women ◽  
Progression Free Survival ◽  
Breast Cancer Prognosis ◽  
Cancer Prognosis ◽  
Prognostic Effect ◽  
H3k27me3 Level ◽  
Glutaminase 1

Abstract Background: Glutaminase 1 (GLS) is a potential therapeutic target for breast cancer; although GLS inhibitors have been developed, only a few subjects responded well to the therapy. Considering that the expression of trimethylation of histone H3 lysine 27 (H3K27me3) and menopausal status have been closely linked to the role of GLS, we tried to examine the modification effects of H3K27me3 and menopausal status on GLS to breast cancer prognosis, which would be helpful to identify the more suitable patients to the GLS inhibitors.Methods: Data for 963 women diagnosed with primary invasive breast cancer between 2008 and 2015 were analyzed. H3K27me3 and GLS expression in tumors were evaluated with tissue microarrays by immunohistochemistry. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) were estimated using univariable and multivariable Cox regression models. The interaction was assessed on multiplicative scale by stratification analysis.Results: After a median follow-up of 70.6 months (interquartile range: 45.6-103.9), we confirmed the association between H3K27me3 and both outcomes (HR =0.57, 95% CI: 0.37-0.86 for OS; HR =0.66, 95% CI: 0.48-0.91 for PFS) and found that the prognostic roles of GLS were not statistically significant in the overall patients. There was a beneficial prognostic effect of GLS expression on OS for those with low H3K27me3 level (HR =0.50, 95% CI: 0.20-1.28) but an adverse prognostic effect for those with high H3K27me3 level (HR =3.90, 95% CI: 1.29-11.78) among premenopausal women, and the interaction was significant (Pinteraction =0.003). Similar pattern was further observed for PFS (HR =0.44, 95% CI: 0.20-0.95 for low H3K27me3 level, HR =1.35, 95% CI: 0.74-2.48 for high H3K27me3 level, Pinteraction =0.024). The interaction didn’t occur among postmenopausal women.Conclusions: This study revealed the modification effects of H3K27me3 and menopausal status on GLS to breast cancer prognosis, which would help optimize the medication strategies related to GLS inhibitors.

scholarly journals Endogenous hormones and risk of invasive breast cancer in pre- and post-menopausal women: findings from the UK Biobank

2021 ◽  
Author(s):  
Sandar Tin Tin ◽  
Gillian K. Reeves ◽  
Timothy J. Key
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Invasive Breast Cancer ◽  
Cox Regression ◽  
Menopausal Status ◽  
Endogenous Hormones ◽  
Uk Biobank ◽  
Menopausal Women ◽  
Post Menopausal

Abstract Background Some endogenous hormones have been associated with breast cancer risk, but the nature of these relationships is not fully understood. Methods UK Biobank was used. Hormone concentrations were measured in serum collected in 2006–2010, and in a repeat subsample (N ~ 5000) in 2012–13. Incident cancers were identified through data linkage. Cox regression models were used, and hazard ratios (HRs) corrected for regression dilution bias. Results Among 30,565 pre-menopausal and 133,294 post-menopausal women, 527 and 2,997, respectively, were diagnosed with invasive breast cancer during a median follow-up of 7.1 years. Cancer risk was positively associated with testosterone in post-menopausal women (HR per 0.5 nmol/L increment: 1.18; 95% CI: 1.14, 1.23) but not in pre-menopausal women (pheterogeneity = 0.03), and with IGF-1 (insulin-like growth factor-1) (HR per 5 nmol/L increment: 1.18; 1.02, 1.35 (pre-menopausal) and 1.07; 1.01, 1.12 (post-menopausal); pheterogeneity = 0.2), and inversely associated with SHBG (sex hormone-binding globulin) (HR per 30 nmol/L increment: 0.96; 0.79, 1.15 (pre-menopausal) and 0.89; 0.84, 0.94 (post-menopausal); pheterogeneity = 0.4). Oestradiol, assessed only in pre-menopausal women, was not associated with risk, but there were study limitations for this hormone. Conclusions This study confirms associations of testosterone, IGF-1 and SHBG with breast cancer risk, with heterogeneity by menopausal status for testosterone.

scholarly journals Height, weight, weight change and risk of breast cancer in Rio de Janeiro, Brazil

2001 ◽  
Vol 119 (2) ◽  
pp. 62-66 ◽  
Author(s):  
Anelise Bezerra de Vasconcelos ◽  
Gulnar Azevedo e Silva Mendonça ◽  
Rosely Sichieri
Keyword(s):  
Breast Cancer ◽  
Weight Loss ◽  
Rio De Janeiro ◽  
Menopausal Status ◽  
Premenopausal Women ◽  
Positive Association ◽  
State University ◽  
Weight Changes ◽  
Potential Risk Factors ◽  
Incident Cases

CONTEXT: The relationship between body size and breast cancer still remains controversial in considering menopausal status. OBJECTIVE: To evaluate the association of height, weight and weight changes with breast cancer in the city of Rio de Janeiro, Brazil. DESIGN: Case-control study. SETTING: National Cancer Institute (INCA), Rio de Janeiro, Brazil, and State University of Rio de Janeiro (UERJ). SAMPLE: 177 incident cases of invasive breast cancer admitted to the main hospital of INCA between May 1995 and February 1996, and 377 controls recruited from among female visitors to the same hospital. MAIN MEASUREMENTS: Height and weight were measured and information on maximum weight, weight at ages 18 and 30 years, and potential risk factors were ascertained by interview at the hospital. RESULTS: Height was not related to risk of breast cancer among both pre and postmenopausal women. Nevertheless, women in this study were shorter than in studies that have found a positive association. Premenopausal women in the upper quartile of recent body mass index (BMI) and maximum BMI showed a reduced risk of breast cancer (P for trend <= 0.03). Weight loss between ages 18 and 30 years and from 18 years to present was also associated with breast cancer among premenopausal women. CONCLUSIONS: These findings may merely indicate the known association between leanness and breast cancer. Further studies should explore the role of weight loss on breast cancer risk.

scholarly journals Prognostic role of GPER/Ezrin in triple-negative breast cancer is associated with menopausal status

2019 ◽  
Vol 8 (6) ◽  
pp. 661-671 ◽  
Author(s):  
Shuang Ye ◽  
Yuanyuan Xu ◽  
Jiehao Li ◽  
Shuhui Zheng ◽  
Peng Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cox Regression ◽  
Menopausal Status ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Survival Prognosis ◽  
Kaplan Meier

The role of G protein-coupled estrogen receptor 1 (GPER) signaling, including promotion of Ezrin phosphorylation (which could be activated by estrogen), has not yet been clearly identified in triple-negative breast cancer (TNBC). This study aimed to evaluate the prognostic value of GPER and Ezrin in TNBC patients. Clinicopathologic features including age, menopausal status, tumor size, nuclear grade, lymph node metastasis, AJCC TNM stage, and ER, PR and HER-2 expression were evaluated from 249 TNBC cases. Immunohistochemical staining of GPER and Ezrin was performed on TNBC pathological sections. Kaplan–Meier analyses, as well as logistic regressive and Cox regression model tests were applied to evaluate the prognostic significance between different subgroups. Compared to the GPER-low group, the GPER-high group exhibited higher TNM staging (P = 0.021), more death (P < 0.001), relapse (P < 0.001) and distant events (P < 0.001). Kaplan–Meier analysis showed that GPER-high patients had a decreased OS (P < 0.001), PFS (P < 0.001), LRFS (P < 0.001) and DDFS (P < 0.001) than GPER-low patients. However, these differences in prognosis were not statistically significant in post-menopausal patients (OS, P = 0.8617; PFS, P = 0.1905; LRFS, P = 0.4378; DDFS, P = 0.2538). There was a significant positive correlation between GPER and Ezrin expression level (R = 0.508, P < 0.001) and the effect of Ezrin on survival prognosis corresponded with GPER. Moreover, a multivariable analysis confirmed that GPER and Ezrin level were both significantly associated with poor DDFS (HR: 0.346, 95% CI 0.182–0.658, P = 0.001; HR: 0.320, 95% CI 0.162–0.631, P = 0.001). Thus, overexpression of GPER and Ezrin may contribute to aggressive behavior and indicate unfavorable prognosis in TNBC; this may correspond to an individual’s estrogen levels.

scholarly journals A treelet transform analysis to relate nutrient patterns to the risk of hormonal receptor-defined breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

2015 ◽  
Vol 19 (2) ◽  
pp. 242-254 ◽  
Author(s):  
Nada Assi ◽  
Aurelie Moskal ◽  
Nadia Slimani ◽  
Vivian Viallon ◽  
Veronique Chajes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Principal Component Analysis ◽  
Lower Risk ◽  
Menopausal Status ◽  
Principal Component ◽  
Component Analysis ◽  
Cox Proportional Hazards ◽  
Hormonal Receptor ◽  
Nutrient Patterns ◽  
Prospective Investigation

AbstractObjectivePattern analysis has emerged as a tool to depict the role of multiple nutrients/foods in relation to health outcomes. The present study aimed at extracting nutrient patterns with respect to breast cancer (BC) aetiology.DesignNutrient patterns were derived with treelet transform (TT) and related to BC risk. TT was applied to twenty-three log-transformed nutrient densities from dietary questionnaires. Hazard ratios (HR) and 95 % confidence intervals computed using Cox proportional hazards models quantified the association between quintiles of nutrient pattern scores and risk of overall BC, and by hormonal receptor and menopausal status. Principal component analysis was applied for comparison.SettingThe European Prospective Investigation into Cancer and Nutrition (EPIC).SubjectsWomen (n 334 850) from the EPIC study.ResultsThe first TT component (TC1) highlighted a pattern rich in nutrients found in animal foods loading on cholesterol, protein, retinol, vitamins B12 and D, while the second TT component (TC2) reflected a diet rich in β-carotene, riboflavin, thiamin, vitamins C and B6, fibre, Fe, Ca, K, Mg, P and folate. While TC1 was not associated with BC risk, TC2 was inversely associated with BC risk overall (HRQ5 v. Q1=0·89, 95 % CI 0·83, 0·95, Ptrend<0·01) and showed a significantly lower risk in oestrogen receptor-positive (HRQ5 v. Q1=0·89, 95 % CI 0·81, 0·98, Ptrend=0·02) and progesterone receptor-positive tumours (HRQ5 v. Q1=0·87, 95 % CI 0·77, 0·98, Ptrend<0·01).ConclusionsTT produces readily interpretable sparse components explaining similar amounts of variation as principal component analysis. Our results suggest that participants with a nutrient pattern high in micronutrients found in vegetables, fruits and cereals had a lower risk of BC.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of outcomes in inflammatory breast cancer

2021 ◽  
Author(s):  
Ouissam Al Jarroudi ◽  
Khalid El Bairi ◽  
Naima Abda ◽  
Adil Zaimi ◽  
Laila Jaouani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Receiver Operating Characteristic ◽  
Inflammatory Breast Cancer ◽  
Operating Characteristic ◽  
Cox Regression ◽  
Menopausal Status ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Prognostic Impact ◽  
Receiver Operating

Background: Inflammatory breast cancer (IBC) is uncommon, aggressive and associated with poor survival outcomes. The lack of prognostic biomarkers and therapeutic targets specific to IBC is an added challenge for clinical practice and research. Inflammatory biomarkers such as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios (NLR and PLR) demonstrated independent prognostic impact for survival in breast cancer. In our study, these biomarkers were investigated in a cohort of patients with nonmetastatic IBC. Methods: A retrospective cohort of 102 IBC patients with nonmetastatic disease was conducted at the Mohammed VI University Hospital (Oujda, Morocco) between January 2010 and December 2014. NLR and PLR were obtained from blood cell count at baseline before neoadjuvant chemotherapy (NACT) from patients’ medical records. The receiver operating characteristic was used to find the optimal cut-off. Correlation between these blood-based biomarkers and response to NACT was analyzed by Chi-squared and Fisher's exact test. Their prognostic value for predicting disease-free survival (DFS) and overall survival (OS) was performed based on Cox regression models. Results: Totally, 102 patients with IBC were included in the analysis. Pathologic complete response (pCR) after NACT, defined by the absence of an invasive tumor in the breast tissues and nodes after surgery (ypT0 ypN0), was observed in eight patients (7.8%). NACT response was found to be associated with menopausal status (p = 0.039) and nodal status (p < 0.001). Patients with a low NLR had a higher pCR rate as compared with the high-NLR group (p = 0.043). However, the pCR rate was not significantly associated with age (p = 0.122), tumor side (p = 0.403), BMI (p = 0.615), histological grade (p = 0.059), hormone receptors status (p = 0.206), human epidermal growth factor receptor 2 (p = 0.491) and PLR (p = 0.096). Pre-treatment blood-based NLR of 2.28 was used as the cut-off value to discriminate between high and low NLR according to the receiver operating characteristic curves. Similarly, a value of 178 was used as the cut off for PLR. Patients with low-NLR had a significantly better 5-year DFS (p < 0.001) and OS (p < 0.001) than the high-NLR group. Moreover, low-PLR was significantly associated with higher DFS (p = 0.001) and OS (p = 0.003). The NLR showed a significant prognostic impact for DFS (HR: 2.57; 95% CI: 1.43–4.61; p = 0.01) and for OS (HR: 2.92; 95% CI: 1.70–5.02; p < 0.001). Similarly, a meaningful association between PLR and 5-year DFS (HR: 1.95; 95% CI: 1.10–3.46; p = 0.021) and OS (HR: 1.82; 95% CI: 1.06–3.14; p = 0.03) was noticed. Conclusions: High NLR and PLR were found associated with reduced DFS and OS in nonmetastatic IBC. Further studies are awaited to confirm these findings.

Abstract 16083: Risk of Preserved versus Reduced Ejection Fraction in Women With and Without History of Breast Cancer: The Pathways Heart Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jamal S Rana ◽  
Heather Greenlee ◽  
Richard Cheng ◽  
Cecile A Laurent ◽  
Hanjie Shen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Ejection Fraction ◽  
Endocrine Therapy ◽  
White Women ◽  
Cox Regression ◽  
Prior History ◽  
Reduced Ejection Fraction ◽  
Increased Risk ◽  
History Of

Introduction: Incidence of heart failure (HF), specifically with preserved ejection fraction (HFpEF), is rising in the general population, yet is understudied. To provide a population-based estimate of HF in breast cancer (BC) survivors, we compared risk of HF in women with and without BC history in the Kaiser Permanente Northern California (KPNC) integrated health system. Methods: Data were extracted from KPNC electronic health records. All invasive BC cases diagnosed from 2005-2013 were identified and matched 1:5 with non-BC controls on birth year, race/ethnicity, and KPNC membership at BC diagnosis. Cox regression models assessed the hazard of HF by EF status: HFpEF (EF ≥ 45%), HF with reduced EF (HFrEF; EF < 45%), and unknown EF. Women with prior history of HF were excluded. Models were adjusted for factors known to affect BC risk or CVD and for prevalent CVD at BC diagnosis. We also examined case subgroups who received cardiotoxic chemotherapy, left-sided radiation therapy, and/or endocrine therapy, versus their controls. Results: A total of 14,804 women diagnosed with invasive BC and with no history of HF were identified and matched to 74,034 women without BC history. Women were on average 61 years at BC diagnosis and 65% white. Women with HFpEF were older and more likely to have hypertension (p<0.05). Among all cases vs. controls, there was increased risk of HFrEF (HR: 1.5, 95% CI: 1.18, 1.98) but not HFpEF or unknown EF (figure). Compared to their controls, women treated with chemotherapy were more than 3-times likely to develop HFrEF (HR: 3.26, 95% CI: 2.2, 4.8) and more than 1.5-times likely to develop HFpEF (HR=1.61, 95% CI: 1.15, 2.24). Women who received left-sided radiation therapy had nearly double the risk of developing HFrEF (HR=1.85, 95% CI: 1.20, 2.84). No associations were found among women who received endocrine therapy. Conclusions: Increased surveillance is warranted for women with BC receiving cardiotoxic chemotherapy for development of both HFrEF and HFpEF.

Real-world analysis of disease progression after CDK 4/6 inhibitor (CDKi) therapy in patients with hormone receptor positive (HR+)/HER2- metastatic breast cancer (MBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13030-e13030
Author(s):  
Malinda West ◽  
Andy Kaempf ◽  
Shaun Goodyear ◽  
Thomas Kartika ◽  
Jessica Ribkoff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Molecular Characteristics ◽  
Rapid Progression ◽  
Hormone Receptor Positive ◽  
Her2 Breast Cancer ◽  
Metastatic Setting ◽  
Increased Risk ◽  
Visceral Disease

e13030 Background: CDKi with endocrine therapy (ET) is approved treatment of metastatic HR+/HER2- breast cancer based on PFS benefit vs ET alone. Outcomes data following CDKi discontinuation (dc) is limited, with trials ongoing in this setting. The reported phenomenon of rapid progression within 4 months of CDKi dc raises concern over CDKi impact on HR+/HER2- MBC biology. This study aims to define outcomes after CDKi dc and identify predictors of progression. Methods: This is a retrospective review of women ≥18 years with HR+/HER2- MBC who received CDKi between 4/1/14 and 12/1/19. Patient and tumor characteristics, pre and post CDKi tx, and reason for CDKi dc were collected. Time to event outcomes from date of CDKi dc (primary = PFS, secondary = Overall Survival, OS) were analyzed with Kaplan Meier estimators and Cox regression. Results: Analysis included 140 patients (median age 65 years), with most MBC (84%) arising from earlier stage disease. 51% of MBCs had visceral disease, and 66% received tx prior to CDKi. The most common CDKi was palbociclib (93%); and most common ET were letrozole (52%) and fulvestrant (40%). Median CDKi tx duration was 9 months (3.5 – 17.4) with 80% dc due to progression. Post CDKi txs included chemotherapy (44%), ET (24%), targeted tx (21%), no further tx (7%) and CDKi tx (4%). Median follow up was 12 months. mPFS post CDKi dc were 6.5 months (95% CI: 5.0 – 7.9) and 11.3 months (95% CI: 4.6 – 23.7) in patients who dc CDKi due to progression or other reasons, respectively (HR 1.77, 95%CI: 1.10-2.85). Among 112 patients who progressed on CDKi, estimated 4-month incidence of post CDKi progression or death was 31% (Table ). mOS post CDKi dc was 15.4 months (95%CI: 13.3-19.0) and mOS post CDKi initiation was 26.5 months (95% CI: 23.3 – 34.3). Visceral disease (HR 1.45, 95%CI: 1.01-2.08) and progression as reason for CDKi dc (HR 1.77, 95%CI: 1.1-2.85) were predictors of PFS (p < 0.05). Receiving fulvestrant with CDKi (HR 1.42, 95%CI: 0.96-1.0), prior chemotherapy in the metastatic setting (HR = 1.39, 95% CI: 0.90 – 2.14), and shorter CDKi duration were associated with non-significant increased risk of PFS. Conclusions: Rapid progression or death at 4 months occurred in 31% of MBCs following CDKi dc due to progression. Ongoing studies to define clinical and molecular characteristics of rapidly progressing tumors are underway to develop targeted tx approaches and improve outcomes.[Table: see text]

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