Long term outcome data from the EORTC 75111-10114 ETF/BCG randomized phase II study: Pertuzumab and trastuzumab with or without metronomic chemotherapy for older patients with HER2-positive metastatic breast cancer, followed by T-DM1 after progression

 

by Hans Wildiers, Thomas Meyskens, Sandrine Marréaud, Lissandra Dal Lago, Peter Vuylsteke, Giuseppe Curigliano, Simon Waters, Barbara Brouwers, Bart Meulemans, Berta Sousa, Coralie Poncet, Etienne Brain 

 

The Breast: Published: May 19, 2022

 

Introduction

Older patients are at higher risk of chemotherapy-induced toxicity, raising interest in less toxic anti-HER2 regimens for older persons with HER2-positive (HER2+) metastatic breast cancer (MBC).

Patients and methods

This phase II study randomized (1:1) patients with HER2+ MBC, aged 70+ or frail 60+, to first line chemotherapy with metronomic oral cyclophosphamide (M) + Trastuzumab (T) and Pertuzumab (P) or TP alone. T-DM1 was offered in case of progression.

Results

In total, 39 and 41 patients were randomized to TP and TPM arm respectively. Median follow-up is 54.0 months. 24-month PFS was 18.7% (95% CI 8.2–32.4) and 28.7% (95% CI 15.8–43.0), respectively. A total of 49 (61.3%) patients died of whom 37 (75.5%) from disease progression; number of deaths per arm was 27 (69.2%) for TP and 22 (53.7%) for TPM. There was no significant difference in OS between the two arms (median OS TP vs TPM: 32.1 vs 37.5 months, p 0.25). Among the 40 patients who have started T-DM1 after disease progression on TP/TPM, PFS rate at 6 months after start of T-DM1 was 43.6% (95% CI: 27.7–58.5) and grade 3 or higher AE occurred in 18 pts (45%).

Conclusions

Metronomic chemotherapy-based dual blockade (TPM), followed by T-DM1 after progression, provides an active and relatively well tolerated treatment option in an older/frail HER2+ MBC population, with a median survival of over 3 years. Nevertheless, the majority of this older/frail population died from breast cancer, highlighting the need for well tolerated and efficacious treatments in these patients.

Breast Surgery Bulletin - April 2022

 

Global guidelines for breast cancer screening: A systematic review

 

by Wenhui Ren, Mingyang Chen, Youlin Qiao, Fanghui Zhao 

 

The Breast: Published: April 19, 2022

 

Highlights

• This systematic review comprehensively maps the recommendations of the latest international breast screening guidelines, providing valuable tools for clinical decision-making in different settings.

• Most guidelines recommended biennial mammographic screening between 40 to 74 years for the average-risk populations and annual MAM or annual MRI starting from a younger age for the high-risk populations. However, there are indeed discrepancies in screening age and method among countries.

• High-quality evidence and rigorous methodology are the keys to guidance development, but current guidelines varied in methodological quality.

Summary

Breast cancer screening guidelines could provide valuable tools for clinical decision-making by reviewing the available evidence and providing recommendations. Little information is known about how many countries have issued breast cancer screening guidelines and the differences among existed guidelines. We systematically reviewed current guidelines and summarized corresponding recommendations, to provide references for good clinical practice in different countries.

 

Factors influencing five-year adherence to adjuvant endocrine therapy in breast cancer patients: A systematic review

by Izzati Yussof, Nor Asyikin Mohd Tahir, Ernieda Hatah, Noraida Mohamed Shah 

 The Breast: Published:January 24, 2022

 Purpose

This systematic review aimed to determine the rate and identify correlates of adherence and persistence over five years of treatment with adjuvant endocrine therapy in female breast cancer patients.

Methods

Relevant articles were identified from Medline, Embase, AMED, PsycINFO, International Pharmaceutical Abstracts, and APA PsycArticles. Studies that measured patient adherence in the implementation or persistence phase for a period of at least five years using objective or multiple measures of adherence and investigated correlates of adherence were included. The titles, abstracts and full articles were screened and reviewed by two authors and any discrepancies were discussed with a third author.

Results

Twenty-six studies were included. Mean rate of adherence at five-year for implementation phase was 66.2% (SD = 17.3%), and mean persistence was 66.8% (SD = 14.5%). On average, adherence decreased by 25.5% (SD = 9.3%) from the first to fifth year. Higher rate of adherence was observed through self-report in comparison to database or medical record. Older age, younger age, higher comorbidity index, depression and adverse effects were associated with lower adherence. Treatment with aromatase inhibitors, received chemotherapy, and prior medication use were associated with improved adherence.

Conclusion

Adherence to adjuvant endocrine therapy decreased from the first to fifth year of treatment. On average, one-third of patients were not adherent to treatment by the fifth year. Nineteen recurring factors were found to be significantly associated with long-term adherence in multiple studies. Further research using objective or multiple measures of adherence are needed to improve validity of results.

 

Mammographic sensitivity as a function of tumor size: a novel estimation based on population-based screening data

 

 Mammographic sensitivity as a function of tumor size: a novel estimation based on population-based screening data

 

by Jing Wang, Pam Gottschal, Lilu Ding, Daniëlle.W.A van Veldhuizen, Wenli Lu, Nehmat Houssami, Marcel J.W. Greuter, Geertruida H. de Bock

 

The Breast: VOLUME  55, P69-74, FEBRUARY 01, 2021

 

Highlights

•Mammographic sensitivity is a key indicator of screening effectiveness.

•Previous model using logistic function might overestimate size-specific sensitivity.

•Our model showed that sensitivity increased from 0 to 85% for tumor sizes from 2 to 20 mm.

•Our model may provide a better representation of data observed in screening programs.

Background

Instead of a single value for mammographic sensitivity, a sensitivity function based on tumor size more realistically reflects mammography’s detection capability. Because previous models may have overestimated size-specific sensitivity, we aimed to provide a novel approach to improve sensitivity estimation as a function of tumor size.

Methods

Using aggregated data on interval and screen-detected cancers, observed tumor sizes were back-calculated to the time of screening using an exponential tumor growth model and a follow-up time of 4 years. From the observed number of detected cancers and an estimation of the number of false-negative cancers, a model for the sensitivity as a function of tumor size was determined. A univariate sensitivity analysis was conducted by varying follow-up time and tumor volume doubling time (TVDT). A systematic review was conducted for external validation of the sensitivity model.

Results

Aggregated data of 22,915 screen-detected and 10,670 interval breast cancers from the Dutch screening program were used. The model showed that sensitivity increased from 0 to 85% for tumor sizes from 2 to 20 mm. When TVDT was set at the upper and lower limits of the confidence interval, sensitivity for a 20-mm tumor was 74% and 93%, respectively. The estimated sensitivity gave comparable estimates to those from two of three studies identified by our systematic review.

Conclusion

Derived from aggregated breast screening outcomes data, our model’s estimation of sensitivity as a function of tumor size may provide a better representation of data observed in screening programs than other models.