Body Mass Index and Hormone Receptor Status Influence Recurrence Risk in HER2-Positive Early Breast Cancer Patients

Cantini, Luca; Pistelli, Mirco; Merloni, Filippo; Fontana, A.; Bertolini, Ilaria; Angelis, Claudia De; Bastianelli, Lucia; Mora, A. Della; Santinelli, Alfredo; Savini, Agnese; Maccaroni, Elena; Diodati, Lucrezia; Falcone, Alfredo; Berardi, Rossana

doi:10.1016/j.clbc.2019.06.008

Cited by 11 publications

(19 citation statements)

References 23 publications

(33 reference statements)

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“…Preclinical studies corroborated that PI3K, MAPK, and NOTCH were significantly overexpressed in HR−/HER2 + breast cancer, which could be potentially correlated to therapeutic resistance and lead to the poor survival outcome [ 41 ]. Indeed, the specific influence of HR status on the overall prognosis of HER2-positive breast cancer remained controversial [ 42 ], and this kind of inconsistency may due to the relatively limited volume of sample size, insufficient follow-up, and the discordance in inclusion criteria. Under this circumstance, this large-scale, population-based study provided strong evidence for the distinctive prognosis of HR-based HER2-poaistive breast cancer population.…”

Section: Discussionmentioning

confidence: 99%

The impact of hormone receptor on the clinical outcomes of HER2-positive breast cancer: a population-based study

Wang

et al. 2022

Int J Clin Oncol

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Background To investigate the impact of hormone receptor (HR) on the clinicopathological characteristics and prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Methods Using the Surveillance, Epidemiology, and End Results database, we enrolled patients diagnosed with HER2-positive breast cancer between 2010 and 2016, which were successively assessed for eligibility and categorized into HR + /HER2 + and HR-/HER2 + subgroups. Clinicopathological characteristics were undergone comparative analyses with the baseline distinctions calibrated by propensity score matching, while the survival outcomes were compared using Kaplan–Meier method with log-rank tests. Results A total of 46,803 HER2-positive breast cancer patients were identified, of which 32,919 individuals were HR + /HER2 + subtype and 13,884 individuals were HR-/HER2 + subtype, respectively. Comparatively, HR + /HER2 + breast cancer presented a lower histological grade, a smaller tumor size, a lower nodal involvement, and a lower rate of de novo stage IV disease. Substantial heterogeneity was detected in the metastatic patterns of organ-specific involvement between the two subgroups with initial metastasis. Overall, patients with HR + /HER2 + tumors had increasingly favorable prognosis in terms of overall survival and breast cancer-specific survival than patients with the HR−/HER2 + subtype. However, this kind of tendency exhibited disparities associated with HR-specific subtypes based on estrogen receptor (ER) and progesterone receptor (PgR) status, in which ER−/PgR + tended to present the worst prognosis. Conclusion This study revealed profound heterogeneity associated with HR status in the clinical outcomes of HER2-positive breast cancer regarding clinicopathological features, metastatic patterns, and prognosis. Prospective studies to optimize therapeutic strategies for HER2-positive subgroups are warranted.

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Section: Discussionmentioning

confidence: 99%

The impact of hormone receptor on the clinical outcomes of HER2-positive breast cancer: a population-based study

Wang

et al. 2022

Int J Clin Oncol

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“…Furthermore, there are many studies in progress investigating the role of adjuvant anti-PD1/PD-L1 therapy in this setting (NCT02926196). So, validated biomarkers are needed to better predict prognosis and to tailor post-surgery treatment decisions as discussed elsewhere [ 21 , 22 ]. Since changes in proliferation anticipate changes in tumor growth rate, Ki67 change might serve as a valuable prognostic marker for patients who do not achieve pCR.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Impact of Ki-67 Change in Locally Advanced and Early Breast Cancer after Neoadjuvant Chemotherapy: A Single Institution Experience

Pistelli

Merloni

Crocetti

et al. 2021

Journal of Oncology

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Systemic neoadjuvant chemotherapy (NCT) is a standard treatment for locally advanced breast cancer (LABC) and for selected early breast cancer (EBC). In these settings, the prognostic and predictive role of Ki-67 before and after NCT is unclear. The aim of our study was to investigate the prognostic role of Ki-67 change in patients not achieving pathological complete response (pCR). We retrospectively analyzed data of patients who did not achieve pCR assessing Ki-67 expression pre- and post-NCT. We stratified three groups: high reduction (>20%), low reduction (1–20%), and no reduction in Ki-67. These groups were correlated with clinical and pathological data by χ2 test. We estimated disease-free survival (DFS) and overall survival (OS) using Kaplan–Meier method, and we adopted univariate and multivariate Cox proportional hazard models. We selected 82 patients from a database of 143 patients, excluding those who were metastatic at diagnosis, achieved pCR, or lack data regarding Ki-67. Median age at diagnosis was 54 years (range 30–75); 51 patients were Luminal B, 10 human epidermal growth factor receptor 2 (HER-2) enriched, and 21 triple negative. A significant correlation between high Ki-67 reduction and luminal B HER-2-negative subtype was observed ( p = 0,0035 ). The change in Ki-67 was significantly associated with DFS ( p = 0,0596 ) and OS ( p = 0,0120 ), also at multivariate analysis ( p = 0,0256 for DFS; p = 0,0093 for OS). In particular, as compared to patients with low/no reduction of Ki-67, those with high Ki-67 reduction (>20%) after NCT showed better survival (60% vs. 56% vs. 83% after 5 years from diagnosis, respectively; p = 0.01 ). In conclusion, in our study, Ki-67 change showed a significant prognostic role in breast cancer patients treated with NCT who did not achieve pCR. Crucially, Ki-67 < 20% identifies a high-risk population that may be eligible for clinical trials with novel therapeutic interventions in adjuvant setting.

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“…Different studies have investigated the association between BMI and the prognosis of HER2+ BC patients receiving adjuvant or neoadjuvant bio-chemotherapy ( Table 1 ). In the adjuvant setting, Cantini et al 118 evaluated the correlation between overweight, defined as a BMI ⩾25 kg/m 2 , and distant-disease-free survival (DDFS) in 279 early-stage (I–III) HER2+ BC patients treated with adjuvant trastuzumab between 2006 and 2016. In this retrospective study, the authors found a significant correlation between high BMI and worse DDFS, which was limited to the HR–/HER2+ BC cohort.…”

Section: Clinical Evidencementioning

confidence: 99%

Prognostic impact of body mass index (BMI) in HER2+ breast cancer treated with anti-HER2 therapies: from preclinical rationale to clinical implications

et al. 2022

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Human Epidermal growth factor Receptor 2 (HER2) overexpression or HER2 gene amplification defines a subset of breast cancers (BCs) characterized by higher biological and clinical aggressiveness. The introduction of anti-HER2 drugs has remarkably improved clinical outcomes in patients with both early-stage and advanced HER2+ BC. However, some HER2+ BC patients still have unfavorable outcomes despite optimal anti-HER2 therapies. Retrospective clinical analyses indicate that overweight and obesity can negatively affect the prognosis of patients with early-stage HER2+ BC. This association could be mediated by the interplay between overweight/obesity, alterations in systemic glucose and lipid metabolism, increased systemic inflammatory status, and the stimulation of proliferation pathways resulting in the stimulation of HER2+ BC cell growth and resistance to anti-HER2 therapies. By contrast, in the context of advanced disease, a few high-quality studies, which were included in a meta-analysis, showed an association between high body mass index (BMI) and better clinical outcomes, possibly reflecting the negative prognostic role of malnourishment and cachexia in this setting. Of note, overweight and obesity are modifiable factors. Therefore, uncovering their prognostic role in patients with early-stage or advanced HER2+ BC could have clinical relevance in terms of defining subsets of patients requiring more or less aggressive pharmacological treatments, as well as of designing clinical trials to investigate the therapeutic impact of lifestyle interventions aimed at modifying body weight and composition. In this review, we summarize and discuss the available preclinical evidence supporting the role of adiposity in modulating HER2+ BC aggressiveness and resistance to therapies, as well as clinical studies reporting on the prognostic role of BMI in patients with early-stage or advanced HER2+ BC.

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Body Mass Index and Hormone Receptor Status Influence Recurrence Risk in HER2-Positive Early Breast Cancer Patients

Cited by 11 publications

References 23 publications

The impact of hormone receptor on the clinical outcomes of HER2-positive breast cancer: a population-based study

The impact of hormone receptor on the clinical outcomes of HER2-positive breast cancer: a population-based study

Prognostic Impact of Ki-67 Change in Locally Advanced and Early Breast Cancer after Neoadjuvant Chemotherapy: A Single Institution Experience

Prognostic impact of body mass index (BMI) in HER2+ breast cancer treated with anti-HER2 therapies: from preclinical rationale to clinical implications

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