Breast Surgery Bulletin: March 2023

 

Tailoring the optimal duration of the extended adjuvant endocrine therapy in patients with early-stage breast cancer. A systematic review and meta-analysis of randomized clinical trials

by Laura Pala, Tommaso De Pas, Eleonora Pagan, Isabella Sala, Chiara Catania, Emma Zattarin, Paolo Arnone, Massimo M. Grassi, Marco Colleoni, Antonio C. Wolff, Javier Cortes, Martine Piccart, Richard D. Gelber, Giuseppe Viale, Vincenzo Bagnardi, Fabio Conforti 

The Breast: Published: March 01, 2023

Background

Controversy exists regarding the optimal duration of the extended adjuvant endocrine treatment (ET) in patients with early-stage breast-cancer (eBC).

We performed a systematic review and trial-level meta-analysis of all randomized clinical trials (RCTs) comparing a “limited-extended” adjuvant ET (defined as more than 5 but less than 7.5 years of treatment overall) versus a “full-extended” adjuvant ET (defined as more than 7.5 years of treatment overall) in eBC.

Methods

To be eligible, RCTs had to i) compare a “limited-extended” adjuvant ET versus a “full-extended” adjuvant ET in patients with eBC; and ii) report disease-free survival (DFS) hazard ratio (HR) according to the disease nodal-status [i.e., nodal-negative (N-ve) versus nodal-positive (N + ve)].

The primary endpoint was to assess the difference in efficacy of full-versus limited-extended ET, measured in terms of the difference in DFS log-HR, according to the disease nodal-status. Secondary endpoint was the difference in efficacy of full-versus limited-extended ET according to tumor size (i.e., pT1 vs pT2/3/4), histological grade (i.e., G1/G2 vs G3), patients’ age (i.e., ≤60 vs > 60 years) and previous type of ET (i.e., aromatase inhibitors vs tamoxifen vs switch strategy).

Results

Three phase III RCTs fulfilled the inclusion criteria. A total of 6689 patients were included in the analysis, of which 3506 (53%) had N + ve disease.

The full-extended ET provided no DFS-benefit as compared with the limited-extended ET in patients with N-ve disease (pooled DFS-HR = 1.04, 95%CI: 0.89 to 1.22; I2 = 18%).

Conversely, in patients with N + ve disease the full-extended ET significantly improved DFS, with a pooled DFS-HR of 0.85 (95%CI: 0.74 to 0.97; I2 = 0%).

There was a significant interaction between the disease nodal-status and the efficacy of the full-versus limited-extended ET (p-heterogeneity = 0.048).

The full-extended ET provided no significant DFS-benefit as compared with the limited-extended ET in all the other subgroups analyzed.

Conclusions

: Patients with eBC and N + ve disease can obtain a significant DFS-benefit from the full-extended as compared with the limited-extended adjuvant ET.

 

 

Breast cancer, breast cancer-directed radiation therapy and risk of hypothyroidism: A systematic review and meta-analysis

 

by Elisabeth Solmunde, Anne Mette Falstie-Jensen, Ebbe L. Lorenzen, Marianne Ewertz, Kristin V. Reinertsen, Olaf M. Dekkers, Deirdre P. Cronin-Fenton 

 

The Breast: Published: February 18, 2023

 

 

Objective

Breast cancer and breast cancer-directed radiation therapy (RT) may increase the risk of late effects, such as hypothyroidism. We conducted a systematic review and meta-analysis to investigate the association between breast cancer, RT, and risk of hypothyroidism in breast cancer survivors.

Methods

Through February 2022, we searched PubMed, EMBASE, and references of relevant articles, to identify papers on breast cancer and breast cancer-directed RT and subsequent risk of hypothyroidism. Articles were screened by title and abstract and reviewed for eligibility. We used a pre-formed data extraction sheet and identified key design elements that could potentially introduce bias. The main outcome was the confounder-adjusted relative risk (RR) of hypothyroidism in breast cancer survivors versus women without breast cancer, and in breast cancer survivors according to the receipt of RT to the supraclavicular lymph nodes. We used a random-effects model to calculate pooled RRs and associated 95% confidence intervals (95% CI).

Results

From 951 papers screened by title and abstract, 34 full-text papers were reviewed for eligibility. We included 20 studies published between 1985 and 2021–19 were cohort studies. Compared with women without breast cancer, the pooled RR of hypothyroidism in breast cancer survivors was 1.48 (95% CI: 1.17, 1.87), with highest risk associated with RT to the supraclavicular region (RR = 1.69, 95% CI: 1.16, 2.46). The most important limitations of the studies were small sample size yielding estimates with low precision, and lack of data on potential confounders.

Conclusion

Breast cancer and radiation therapy to the supraclavicular lymph nodes is associated with an increased risk of hypothyroidism.

 

A systematic review and meta-analysis of BRCA1/2 mutation for predicting the effect of platinum-based chemotherapy in triple-negative breast cancer

 

by Xiaomeng Jia, Kainan Wang, Lingzhi Xu, Ning Li, Zuowei Zhao, Man Li 

 

The Breast: September 02, 2022

Introduction

Platinum-based chemotherapy (PBC) remains the mainstay of treatments for triple-negative breast cancer (TNBC). TNBC is a heterogeneous group, the issue of whether BRCA1/2 mutation carriers have a particular sensitivity to platinum agents is inconclusive. We conducted a meta-analysis to explore the relationship between BRCA1/2 mutation and PBC susceptibility in individuals with TNBC, aiming to gain more information on the size of the benefit of PBC in BRCA1/2 mutation carriers.

Materials and methods

All studies applying PBC with a subgroup of BRCA1/2 status were included. All endpoints, including pCR and RCB in the neoadjuvant phase, DFS in the adjuvant phase, ORR, PFS, and OS in the advanced phase, were assessed using HRs and 95% Cl.

Results

From the 22 studies included, there were 2158 patients with TNBC, with 392 (18%) bearing the BRCA1/2 gene mutation. Based on 13 studies applying neoadjuvant PBC, we discovered that BRCA1/2 mutation was substantially associated with a 17.6% increased pCR rate (HR 1.32, 95% CI 1.17–1.49, p < 0.00001; I2 = 51%). Same result was observed in RCB0/I index (HR 1.38, 95% CI 1.08–1.76, P = 0.009; I2 = 0%). The meta-analysis of 6 trials addressing advanced therapy revealed that ORR rates were significantly higher in patients with BRCA1/2 mutation (HR 1.91, 95% CI 1.48–2.47, p < 0.00001; I2 = 32%), as well as PFS(HR 1.13, 95% CI 0.81–1.57, P = 0.47; I2 = 0%) and OS (HR 1.89, 95% CI 1.22–2.92, P = 0.004; I2 = 0%).

Conclusion

According to our meta-analysis of 22 trials in TNBC, BRCA1/2 mutation carriers were significantly more sensitive to PBC regimens, especially in neoadjuvant and advanced therapy.

 

Effects of physical exercise on cognitive function of breast cancer survivors receiving chemotherapy: A systematic review of randomized controlled trials

by Xiaohan Ren, Xiaoqin Wang, Jiaru Sun, Zhaozhao Hui, Shuangyan Lei, Caihua Wang, Mingxu Wang 

The Breast: Published: March 27, 2022

Background

Cognitive impairment has a great negative impact on quality of life for breast cancer survivors. Emerging evidence suggested that physical exercise can improve cognitive function in order adults with Alzheimer's disease. However, less is known about the effects of physical exercise on cognitive function for breast cancer survivors. The purpose of this meta-analysis was to evaluate the effect of physical exercise on cognitive function in breast cancer survivors.

Methods

EMBASE, the Cochrane Library, Web of Science and PubMed were searched from the establishment of the databases to June 2021. Randomized controlled trials were included. All analysis were conducted using the Revman 5.3.

Results

12 studies (936 participants) indicated that exercise improved self-reported cognitive function (MD 10.12, 95% CI [5.49,14.76], p < 0.0001), cognitive fatigue (MD -5.41, 95% CI [-10.31,-0.51], p = 0.03) and executive function (MD -13.63, 95% CI [-21.86,-5.39], p = 0.0001).

Conclusion

Physical exercise can improve cognitive function for breast cancer survivors, particularly in self-reported cognitive function, and executive function. Future studies need to explore the effect of exercise on cognitive function from the frequency and duration of exercise.

Breast Surgery Bulletin: August 2021

 

Breast cancer screening using synthesized two-dimensional mammography: A systematic review and meta-analysis

 

by Baoqi Zeng, Kai Yu, Le Gao, Xueyang Zeng, Qingxin Zhou 

 

The Breast: Published, July 21, 2021

 

Purpose

We conducted a systematic review and meta-analysis to compare the screening performance of synthesized mammography (SM) plus digital breast tomosynthesis (DBT) with digital mammography (DM) plus DBT or DM alone.

Methods

Medline, Embase, Web of Science, and the Cochrane Library databases were searched from January 2010 to January 2021. Eligible population-based studies on breast cancer screening comparing SM/DBT with DM/DBT or DM in asymptomatic women were included. A random-effect model was used in this meta-analysis. Data were summarized as risk differences (RDs), with 95 % confidence intervals (CIs).

Results

Thirteen studies involving 1,370,670 participants were included. Compared with DM/DBT, screening using SM/DBT had similar breast cancer detection rate (CDR) (RD = −0.1/1000 screens, 95 % CI = −0.4 to 0.2, p = 0.557, I2 = 0 %), but lower recall rate (RD = −0.56 %, 95 % CI = −1.03 to −0.08, p = 0.022, I2 = 90 %) and lower biopsy rate (RD = −0.33 %, 95 % CI = −0.56 to −0.10, p = 0.005, I2 = 78 %). Compared with DM, SM/DBT improved CDR (RD = 2.0/1000 screens, 95 % CI = 1.4 to 2.6, p < 0.001, I2 = 63 %) and reduced recall rate (RD = −0.95 %, 95 % CI = −1.91 to −0.002, p = 0.049, I2 = 99 %). However, SM/DBT and DM had similar interval cancer rate (ICR) (RD = 0.1/1000 screens, 95 % CI = −0.6 to 0.8, p = 0.836, I2 = 71 %) and biopsy rate (RD = −0.05 %, 95 % CI = −0.35 to 0.24, p = 0.727, I2 = 93 %).

Conclusions

Screening using SM/DBT has similar breast cancer detection but reduces recall and biopsy when compared with DM/DBT. SM/DBT improves CDR when compared with DM, but they have little difference in ICR. SM/DBT could replace DM/DBT in breast cancer screening to reduce radiation dose.

Adjuvant CDK4/6 inhibitors combined with endocrine therapy in HR-positive, HER2-negative early breast cancer: A meta-analysis of randomized clinical trials

 

Adjuvant CDK4/6 inhibitors combined with endocrine therapy in HR-positive, HER2-negative early breast cancer: A meta-analysis of randomized clinical trials

 

by Hong-Fei Gao, Ying-Yi Lin, Teng Zhu, Fei Ji, Liu-Lu Zhang, Ci-Qiu Yang, Mei Yang, Jie-Qing Li, Min-Yi Cheng, Kun Wang 

 

The Breast: VOLUME 59, P165-175, OCTOBER 01, 2021

 

Background

The benefit of adjuvant cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors with endocrine therapy (ET) in hormone receptor-positive, human epidermal growth factor 2 receptor-negative (HR+/HER2-) early breast cancer (EBC) is uncertain. Hence, we performed a meta-analysis to determine the efficacy and safety of adjuvant CDK4/6 inhibitors plus ET and to identify potential preferred subpopulations for this regimen.

Methods

A literature search was conducted in PubMed, Embase, Cochrane databases up to Jan 15, 2021. Hazard ratios (HRs) for invasive disease-free survival (IDFS) and risk ratios (RRs) for grade 3/4 adverse events (AEs) and treatment discontinuation were extracted. Analysis with predefined subgroup variables was done. Trial sequential analysis (TSA) was performed to assess the conclusiveness of survival outcomes.

Results

Three trials were eligible (N = 12647). Compared with ET, adjuvant CDK4/6 inhibitors with ET prolonged IDFS in patients with HR+/HER2- EBC (HR 0.87, 95% CI 0.76–0.98, p = 0.03, I2 = 19%), with positive therapeutic responses observed in patients with N2/N3 nodal status (HR 0.83, 95% CI 0.71–0.97, p = 0.02, I2 = 0%). None of the cumulative z-curves crossed the trial monitoring boundaries in TSA, and no reliable conclusion could be drawn. The combination treatment carried a higher risk of grade 3/4 AEs (RR 4.14, 95% CI 3.33–5.15, p < 0.00001) and an increase in treatment discontinuation due to AEs (RR 19.16, 95% CI 9.27–39.61, p < 0.00001).

Conclusions

Adjuvant CDK4/6 inhibitors with ET might provide survival benefit in HR+/HER2- EBC. A statistically significantly improved IDFS was only observed in N2/N3 subgroup. However, overall evidence favoring the use of this combination regimen was inadequate.

Preoperative non-palpable breast lesion localization, innovative techniques and clinical outcomes in surgical practice: a systematic review and meta-analysis

 

Preoperative non-palpable breast lesion localization, innovative techniques and clinical outcomes in surgical practice: a systematic review and meta-analysis

 

by Francesco Garzotto, Rosanna Irene Comoretto, Silvia Michieletto, Gianpaolo Franzoso, Marcello Lo Mele, Dario Gregori, Maria Giuseppina Bonavina, Fernando Bozza, Francesca Caumo, Tania Saibene 

The Breast: VOLUME 58, P93-105, AUGUST 01, 2021

Highlights

•Positioning and localization of reflectors' is nearly of the 100% rate of success. Overall, positive margins rates were 12% (8–17%).

•The re-excision and clear margins rates were 12% (95% CI, 8–17%) and 87% (80–92%), respectively.

•Comparing NWNI and WGL techniques, positive margin rate is lower for the first one and re-excision rate is slightly higher using the latter.

•This technology overcomes the limitations related to other techniques: migrations, the coordination between radiology and surgery, the use of radioactive substances.

•The procedure is comfortable for the radiologist while allow surgeon at resecting the non-palpable lesions ensuring clear margins, avoiding the re-excisions.

•The cosmetic outcome can be obtained minimizing the resection of healthy-tissue.

Abstract

Pre-operative localization of non-palpable breast lesions with non-wired non-ionizing (NWNI) techniques may improve clinical outcomes as reoperation rate, cosmetic outcome and contribute to organizational aspects improvement in breast-conserving surgery (BCS). However only limited literature is available and clinical studies involving these forefront devices are often small and non-randomized. Furthermore, there is a lack of consensus on free margins and cosmetic outcomes definitions. The objective of the present meta-analysis was to determine the crude clinical outcomes reported for the NWNI techniques on BCS. A literature search was performed of PubMed, Embase and Scopus databases up to February 2021 in order to select all prospective or retrospective clinical trials on pre-operative breast lesion localization done with NWNI devices. All studies were assessed following the PRISMA recommendations. Continuous outcomes were described in averages corrected for sample size, while binomial outcomes were described using the weighted average proportion.

Twenty-seven studies with a total of 2103 procedures were identified. The technique is consolidated, showing for both reflectors’ positioning and localization nearly the 100% rate of success. The re-excision and clear margins rates were 14% (95% CI, 11–17%) and 87% (80–92%), respectively. Overall, positive margins rates were 12% (8–17%). In studies that compared NWNI and wire localization techniques, positive margin rate is lower for the first techniques (12%, 6–22% vs 17%, 12–23%) and re-excision rate is slightly higher using the latter (13%, 9–19% vs 16%, 13–18%).

Pre-operative NWNI techniques are effective in the localization of non-palpable breast lesions and are promising in obtaining clear (or negative) margins minimizing the need for re-excision and improving the cosmetic outcomes. Randomized trials are needed to confirm these findings.