Thursday 30 March 2023

Breast Surgery Bulletin - April 2023

 

Patients’ experiences with pre-test genetic counseling provided by breast cancer healthcare professionals: Results from a large prospective multicenter study

by K. Bokkers, E.M.A. Bleiker, M.E. Velthuizen, R. Koelemij, J.P.J. Burgmans, J.H. Klinkenbijl, A.P. Schouten van der Velden, N. Vermulst, B.F. Huizinga, A.J. Witkamp, T. Frakking, R.M. Brohet, C.M. Aalfs, W. Koole, E.J.P. Schoenmaeckers, M.G.E.M. Ausems 

The Breast: Published: March 29, 2023

Background

Pre-test genetic counseling of patients with breast cancer is increasingly being offered by non-genetic healthcare professionals. We aimed to evaluate the experiences of patients with breast cancer receiving pre-test genetic counseling from a non-genetic healthcare professional (i.e., surgeon or nurse).

Methods

Patients who were diagnosed with breast cancer and received pre-test counseling from their surgeon or nurse (mainstream group), and patients who received pre-test counseling from a clinical geneticist (usual care group) were invited to participate in our multicenter study. Between September 2019 and December 2021, patients received a questionnaire after pre-test counseling (T0) and four weeks after receiving their test results (T1) to evaluate psychosocial outcomes, knowledge, discussed topics and satisfaction.

Results

We included 191 patients in our mainstream and 183 patients in our usual care group and received, respectively 159 and 145 follow-up questionnaires. Levels of distress and decisional regret were comparable in both groups. Decisional conflict was higher in our mainstream group (p = 0.01), but only 7% had clinically relevant decisional conflict (vs 2% in usual care group). The possible implications of a genetic test on (secondary) breast or ovarian cancer risks were less frequently discussed in our mainstream group (p = 0.03 and p = 0.000, respectively). In both groups knowledge about genetics was comparable, satisfaction was high and the majority of patients in both groups preferred to give both verbal and written consent for genetic testing.

Conclusion

Mainstreamed genetic care provides sufficient information for the majority of breast cancer patients to decide about genetic testing with minimal distress.

 

Optimising post-operative radiation therapy after oncoplastic and reconstructive procedures

by Trine Tramm, Orit Kaidar-Person 

The Breast: Published: March 28, 2023

Abstract

Surgical techniques for breast cancer have been refined over the past decades to deliver an aesthetic outcome as close as possible to the contralateral intact breast. Current surgery further allows excellent aesthetic outcome even in case of mastectomy, by performing skin sparing or nipple sparing mastectomy in combination with reconstruction. In this review we discuss how to optimise post-operative radiation therapy after oncoplastic and breast reconstructive procedures, including dose, fractionation, volumes, surgical margins, and boost application.

Highlights

• New surgical procedures for breast cancer poses new challenges for the radiation oncologists.

• Oncoplastic breast surgery may question the ability to apply or the need for a tumour bed boost.

• Skin sparing/nipple sparing mastectomies should be planned to assure clear superficial margins.

• Radiation therapy indications, target volumes, dose and fractionation should be adapted per case to provide maximal clinical benefit and reduce toxicity.

• Multidisciplinary teamwork is needed from the time of diagnosis to plan the most appropriate locoregional therapy.

 

Tissue- and liquid biopsy-based biomarkers for immunotherapy in breast cancer

by Luca Licata, Marco Mariani, Federico Rossari, Giulia Viale, Giulia Notini, Matteo Maria Naldini, Carlo Bosi, Marta Piras, Matteo Dugo, Giampaolo Bianchini 

The Breast: Published: March 27, 2023

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and now represent the mainstay of treatment for many tumor types, including triple-negative breast cancer and two agnostic registrations. However, despite impressive durable responses suggestive of an even curative potential in some cases, most patients receiving ICIs do not derive a substantial benefit, highlighting the need for more precise patient selection and stratification. The identification of predictive biomarkers of response to ICIs may play a pivotal role in optimizing the therapeutic use of such compounds. In this Review, we describe the current landscape of tissue and blood biomarkers that could serve as predictive factors for ICI treatment in breast cancer.

The integration of these biomarkers in a “holistic” perspective aimed at developing comprehensive panels of multiple predictive factors will be a major step forward towards precision immune-oncology.

 

Pathologic response and residual tumor cellularity after neo-adjuvant chemotherapy predict prognosis in breast cancer patients

by Damiano Gentile, Andrea Sagona, Camilla De Carlo, Bethania Fernandes, Erika Barbieri, Simone Di Maria Grimaldi, Flavia Jacobs, Giulia Vatteroni, Lorenzo Scardina, Ersilia Biondi, Valeriano Vinci, Rubina Manuela Trimboli, Daniela Bernardi, Corrado Tinterri 

The Breast: Published: March 27, 2023

Introduction

Residual tumor cellularity (RTC) and pathologic complete response (pCR) after neo-adjuvant chemotherapy (NAC) are prognostic factors associated with improved outcomes in breast cancer (BC). However, the majority of patients achieve partial pathologic response (pPR) and no clear correlation between RTC patterns and outcomes was described. Our aims were to define predictive factors for pCR and compare different outcomes of patients with pCR or pPR and with different RTC patterns.

Materials and methods

Baseline and post-NAC demographics, clinicopathological characteristics, post-operative data, survival and recurrence status were recorded from our institutional database. A multivariable analysis was performed using a logistic regression model to identify independent predictors of pCR. Disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) analyses were performed using the Kaplan-Meier method.

Results

Overall, of the 495 patients analyzed, 148 (29.9%) achieved pCR, 347 (70.1%) had pPR, and the median RTC was 40%. Multivariable analysis identified 3 independent factors predictive of pCR: tumor stage before NAC (cT1-2 84.5% versus cT3-4 15.5%), BC sub-type (HER2-positive 54.7% versus triple-negative 29.8% versus luminal-like 15.5%), and vascular invasion (absence 98.0% versus presence 2.0%). We found statistically significant longer DFS, DDFS, and OS in patients with pCR and with RTC <40%; no difference was observed in terms of OS between RTC <40% and RTC ≥40% groups.

Conclusions

Tumor stage before NAC, BC sub-type, and vascular invasion are significant and independent factors associated with pCR. Patients with pCR and with RTC <40% have longer DFS, DDFS, and OS compared with patients with pPR.

 

 

 

Real-world comparative effectiveness of palbociclib plus letrozole versus letrozole in older patients with metastatic breast cancer

by Hope S. Rugo, Xianchen Liu, Benjamin Li, Lynn McRoy, Rachel M. Layman, Adam Brufsky 

The Breast: Published: March 27, 2023

Background

Palbociclib, the first available cyclin-dependent kinase 4/6 inhibitor, plus endocrine therapy is approved for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC). This study compared real-world effectiveness of palbociclib plus letrozole versus letrozole in older patients with MBC in US clinical practice.

Methods

This retrospective analysis included patients from the Flatiron Health longitudinal database. Overall, 796 women with HR+/HER2- MBC aged ≥65 years starting palbociclib plus letrozole or letrozole as first-line therapy between February 2015 and September 2018 were included. Patients were evaluated from treatment start until December 2018, death, or last visit, whichever came first. Real-world progression-free survival (rwPFS), overall survival (OS), and real-world best tumor responses (rwBTR) were endpoints. Stabilized inverse probability treatment weighting (sIPTW) balanced patient characteristics.

Results

After sIPTW, 450 patients treated with palbociclib plus letrozole and 335 treated with letrozole were included; median age was 74.0 years. Median rwPFS was 22.2 (95% CI, 20.0–30.4) months for palbociclib plus letrozole versus 15.8 (12.9–18.9) months for letrozole (hazard ratio, 0.59 [0.47–0.74]; P < 0.001). Median OS was not reached for palbociclib plus letrozole versus 43.4 months (30.0-not estimable) with letrozole (hazard ratio, 0.55 [0.42–0.72]; P < 0.001). No interactions between age groups (65–74 and ≥ 75 years) and treatment groups were observed for rwPFS or OS. Rate of rwBTR was significantly higher for palbociclib plus letrozole (52.4%) versus letrozole (22.1%; odds ratio, 2.0 [1.4–2.7]; P < 0.001).

Conclusion

This analysis demonstrates the effectiveness of palbociclib combination therapy as standard-of-care for older patients with HR+/HER2- MBC in the first-line setting.

 

Future potential targets of antibody-drug conjugates in breast cancer

 

by Chiara Corti, Luca Boscolo Bielo, Ambra Carnevale Schianca, Beatrice Taurelli Salimbeni, Carmen Criscitiello, Giuseppe Curigliano 

 

The Breast: VOLUME 69, P312-322, JUNE 2023 (Published: March 24, 2023)

 

Abstract

Metastatic breast cancer (BC) remains an incurable disease. Besides endocrine and targeted agents, chemotherapy is still a relevant therapeutic option for this disease. Recently, antibody-drug conjugates (ADCs) have shown to overcome the lack of tumor specificity and systemic toxicity typically associated with traditional chemotherapies, thus improving the therapeutic index. To effectively exploit this technological breakthrough, identification of optimal target antigens (Ags) is of utmost importance. To make the ideal target, differential expression of target Ags between healthy and cancer tissues, as well as specific mechanisms of ADC internalization after Ag-antibody interaction are required.

Therefore, several in silico strategies to identify and characterize new promising candidate Ags have been developed. If initial in vitro and in vivo positive data are documented, thus providing a biological rationale for further Ag investigation, early phase clinical trials are designed. In BC, these strategies have already led to the development of effective ADCs, namely trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), primarily targeting HER2 and TROP-2. However, promising new Ags are currently under investigation, with encouraging results especially coming from targeting HER3, FRα, Tissue Factor, LIV-1, ROR1-2, and B7–H4.

In this review, we describe the landscape of emergent and future potential targets (i.e., other than HER2 and TROP-2) investigated in BC for ADC development. Predominant target expression, function, preclinical rationale, potential clinical implication, as well as preliminary clinical trial results are provided.

 

Early increase in tamoxifen dose in CYP2D6 poor metaboliser breast cancer patients and survival: A propensity score matching analysis

 

by Isabel Blancas, Marina Linares-Rodríguez, Eduardo Martínez de Dueñas, Carmen Herrero-Vicent, María D. Molero-Mir, José M. Garrido, Fernando Rodríguez-Serrano 

 

The Breast: Published: March 23, 2023

 

Purpose

Tamoxifen is a drug used for hormone receptor-positive breast cancers, primarily metabolised by the CYP2D6 enzyme into active metabolites such as endoxifen. CYP2D6 displays varying degrees of activity depending on its genotype. This study aims to analyse the effect of an early increase in tamoxifen dose in poor metabolisers (PM) on survival.

Methods

We enrolled 220 patients diagnosed with breast cancer who were treated with tamoxifen. CYP2D6 polymorphisms were determined, and the phenotype was estimated according to the Clinical Pharmacogenetics Implementation Consortium. Disease-free survival (DFS) and overall survival (OS) were analysed considering the entire patient group, and a subgroup of 110 patients selected by Propensity Score Matching (PSM). All women were treated with 20 mg/day of tamoxifen for 5 years, except PM, who initially received 20 mg/day for 4 months, followed by 40 mg/day for 4 months and 60 mg/day for 4 months before returning to the standard dose of 20 mg/day until completing 5 years of treatment.

Results

The analysis of the influence of CYP2D6 polymorphisms in the complete group and in the PSM subgroup revealed no significant differences for DFS or OS. Furthermore, DFS and OS were analysed in relation to various covariates such as age, histological grade, nodal status, tumour size, HER-2, Ki-67, chemotherapy, and radiotherapy. Only age, histological grade, nodal status, and chemotherapy treatment demonstrated statistical significance.

Conclusion

An early increase in tamoxifen dose in PM patients is not associated with survival differences among CYP2D6 phenotypes.

 

 

 

 

Mammographic density and interval cancers in mammographic screening: Moving towards more personalized screening

by Marthe Larsen, Elsebeth Lynge, Christoph I. Lee, Kristina Lång, Solveig Hofvind 

The Breast: VOLUME 69, P306-311, JUNE 2023 (Published: March 21, 2023)

Purpose

The European Society on Breast Imaging has recommended supplemental magnetic resonance imaging (MRI) every two to four years for women with mammographically dense breasts. This may not be feasible in many screening programs. Also, the European Commission Initiative on Breast Cancer suggests not implementing screening with MRI. By analyzing interval cancers and time from screening to diagnosis by density, we present alternative screening strategies for women with dense breasts.

Methods

Our BreastScreen Norway cohort included 508 536 screening examinations, including 3125 screen-detected and 945 interval breast cancers. Time from screening to interval cancer was stratified by density measured by an automated software and classified into Volpara Density Grades (VDGs) 1–4. Examinations with volumetric density ≤3.4% were categorized as VDG1, 3.5%–7.4% as VDG2, 7.5%–15.4% as VDG3, and ≥15.5% as VDG4. Interval cancer rates were also determined by continuous density measures.

Results

Median time from screening to interval cancer was 496 (IQR: 391–587) days for VDG1, 500 (IQR: 350–616) for VDG2, 482 (IQR: 309–595) for VDG3 and 427 (IQR: 266–577) for VDG4. A total of 35.9% of the interval cancers among VDG4 were detected within the first year of the biennial screening interval. For VDG2, 26.3% were detected within the first year. The highest annual interval cancer rate (2.7 per 1000 examinations) was observed for VDG4 in the second year of the biennial interval.

Conclusions

Annual screening of women with extremely dense breasts may reduce the interval cancer rate and increase program-wide sensitivity, especially in settings where supplemental MRI screening is not feasible.

 

Radiotherapy including a boost should be delivered over no more than 3–4 weeks invited article for the Breast's upcoming SI “de-escalation of loco-regional treatment in breast cancer: Time to find the balance?” the role of the radiation therapy breast boost in the 2020s

by M. Dzhugashvili, L. Veldeman, A.M. Kirby 

The Breast: VOLUME 69, P299-305, JUNE 2023 (Published:March 17, 2023)

Abstract

Given that most local relapses of breast cancer occur proximal to the original location of the primary, the delivery of additional radiation dose to breast tissue that contained the original primary cancer (known as a “boost”) has been a standard of care for some decades. In the context of falling relapse rates, however, it is an appropriate time to re-evaluate the role of the boost. This article reviews the evolution of the radiotherapy boost in breast cancer, discussing who to boost and how to boost in the 2020s, and arguing that, in both cases, less is more.

Highlights

•Delivery of additional RT dose to breast tumour bed has a sound pathological basis.

•Breast boost local relapse benefits vary according to clinicopathological risk factors.

•Young age, high grade & triple negative phenotype are key eligibility criteria.

•There is no survival benefit from a tumour bed boost in breast RT.

•The boost target volume and treatment burden should be minimised.

Thursday 2 March 2023

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.

 

 

Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial

 

The Lancet Oncology:  VOLUME 24, ISSUE 3, P273-285, MARCH 2023

 

Background

We aimed to report on long-term outcomes of patients with small, node-negative, HER2-positive breast cancer treated with adjuvant paclitaxel and trastuzumab and to establish potential biomarkers to predict prognosis.

Methods

In this open-label, single-arm, phase 2 study, patients aged 18 years or older, with small (≤3 cm), node-negative, HER2-positive breast cancer, and an Eastern Cooperative Oncology Group performance status of 0–1, were recruited from 16 institutions in 13 cities in the USA. Eligible patients were given intravenous paclitaxel (80 mg/m2) with intravenous trastuzumab (loading dose of 4 mg/kg, subsequent doses 2 mg/kg) weekly for 12 weeks, followed by trastuzumab (weekly at 2 mg/kg or once every 3 weeks at 6 mg/kg) for 40 weeks to complete a full year of trastuzumab. The primary endpoint was 3-year invasive disease-free survival. Here, we report 10-year survival outcomes, assessed in all participants who received protocol-defined treatment, with exploratory analyses using the HER2DX genomic tool. This study is registered on ClinicalTrials.gov, NCT00542451, and is closed to accrual.

Findings

Between Oct 29, 2007, and Sept 3, 2010, 410 patients were enrolled and 406 were given adjuvant paclitaxel and trastuzumab and included in the analysis. Mean age at enrolment was 55 years (SD 10·5), 405 (99·8%) of 406 patients were female and one (0·2%) was male, 350 (86·2%) were White, 28 (6·9%) were Black or African American, and 272 (67·0%) had hormone receptor-positive disease. After a median follow-up of 10·8 years (IQR 7·1–11·4), among 406 patients included in the analysis population, we observed 31 invasive disease-free survival events, of which six (19·4%) were locoregional ipsilateral recurrences, nine (29·0%) were new contralateral breast cancers, six (19·4%) were distant recurrences, and ten (32·3%) were all-cause deaths. 10-year invasive disease-free survival was 91·3% (95% CI 88·3–94·4), 10-year recurrence-free interval was 96·3% (95% CI 94·3–98·3), 10-year overall survival was 94·3% (95% CI 91·8–96·8), and 10-year breast cancer-specific survival was 98·8% (95% CI 97·6–100). HER2DX risk score as a continuous variable was significantly associated with invasive disease-free survival (hazard ratio [HR] per 10-unit increment 1·24 [95% CI 1·00–1·52]; p=0·047) and recurrence-free interval (1·45 [1·09–1·93]; p=0·011).

Interpretation

Adjuvant paclitaxel and trastuzumab is a reasonable treatment standard for patients with small, node-negative, HER2-positive breast cancer. The HER2DX genomic tool might help to refine the prognosis for this population.

 

Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscopy ‘Histolog® scanner’ for breast margin assessment in comparison with conventional specimen radiography

by Riku Togawa, Johanna Hederer, Moira Ragazzi, Thomas Bruckner, Sarah Fastner, Christina Gomez, André Hennigs, Juliane Nees, André Pfob, Fabian Riedel, Benedikt Schäfgen, Anne Stieber, Michael P. Lux, Jörg Heil, Michael Golatta 

The Breast: Published: February 22, 2023

 

Purpose

The Histolog® Scanner (SamanTree Medical SA, Lausanne, Switzerland) is a large field-of-view confocal laser scanning microscope designed to allow intraoperative margin assessment by the production of histological images ready for assessment in the operating room. We evaluated the feasibility and the performance of the Histolog® Scanner (HS) to correctly identify infiltrated margins in clinical practice of lumpectomy specimens. It was extrapolated if the utilization of the HS has the potential to reduce infiltrated margins and therefore reduce re-operation rates in patients undergoing breast conserving surgery (BCS) due to a primarily diagnosed breast cancer including ductal carcinoma in situ.

Methods

This is a single-center, prospective, non-interventional, diagnostic pilot study including 50 consecutive patients receiving BCS. The complete surface of the specimen was scanned using the HS intraoperatively. The surgery and the intraoperative margin assessment of the specimen was performed according to the clinical routine consisting of conventional specimen radiography as well as the clinical impression of the surgeon. Three surgeons and an experienced pathologist assessed the scans produced by the HS for cancer cells on the surface. The potential of the HS to correctly identify involved margins was compared to the results of the conventional specimen radiography alone as well as the clinical routine. The histopathological report served as the gold standard.

Results

50 specimens corresponding to 300 surfaces were scanned by the HS. The mean sensitivity of the surgeons to identify involved margins with the HS was 37.5% ± 5.6%, the specificity was 75.2% ± 13.0%. The assessment of resection margins by the pathologist resulted in a sensitivity of 37.5% and a specificity of 81.0%, while the local clinical routine resulted in a sensitivity of 37.5% and a specificity of 78.2%.

Conclusion

Acquisition of high-resolution histological images using the HS was feasible in clinical practice. Sensitivity and specificity were comparable to clinical routine. With more specific training and experience on image interpretation and acquisition, the HS may have the potential to enable more accuracy in the margin assessment of BCS specimens.

 

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.

 

Diagnostic accuracy of a three-protein signature in women with suspicious breast lesions: a multicenter prospective trial

Breast Cancer Research volume 25, Article number: 20 (2023) 

 

Background

Mammography screening has been proven to detect breast cancer at an early stage and reduce mortality; however, it has low accuracy in young women or women with dense breasts. Blood-based diagnostic tools may overcome the limitations of mammography. This study assessed the diagnostic performance of a three-protein signature in patients with suspicious breast lesions.

Findings

This trial (MAST; KCT0004847) was a prospective multicenter observational trial. Three-protein signature values were obtained using serum and plasma from women with suspicious lesions for breast malignancy before tumor biopsy. Additionally, blood samples from women who underwent clear or benign mammography were collected for the assays. Among 642 participants, the sensitivity, specificity, and overall accuracy values of the three-protein signature were 74.4%, 66.9%, and 70.6%, respectively, and the concordance index was 0.698 (95% CI 0.656, 0.739). The diagnostic performance was not affected by the demographic features, clinicopathologic characteristics, and co-morbidities of the participants.

Conclusions

The present trial showed an accuracy of 70.6% for the three-protein signature. Considering the value of blood-based biomarkers for the early detection of breast malignancies, further evaluation of this proteomic assay is warranted in larger, population-level trials.

This Multi-protein Assessment using Serum to deTermine breast lesion malignancy (MAST) was registered at the Clinical Research Information Service of Korea with the identification number of KCT0004847 (https://cris.nih.go.kr).

 

Cost-effectiveness of sacituzumab govitecan versus chemotherapy in advanced or metastatic triple-negative breast cancer

by Yitian Lang, Qingqing Chai, Wenqi Tao, Yahui Liao, Xiaoyan Liu, Bin Wu 

The Breast: Published: February 09, 2023

Purpose

The ASCENT trial demonstrated the efficacy of sacituzumab govitecan for the treatment of advanced or metastatic triple-negative breast cancer (TNBC). The current study evaluated the cost-effectiveness of receiving sacituzumab govitecan compared with standard of care chemotherapy from the United States payer perspective.

 

Methods

A partitioned survival approach was used to project the disease course of advanced or metastatic TNBC. Two survival modes were applied to analyze two groups of patients. The survival data were gathered from the ASCENT trial. Direct medical costs were derived from the data of Centers for Medicare & Medicaid Services. Utility data was collected from the published literature. The incremental cost-utility ratio (ICUR) was the primary outcome that measured the cost-effectiveness of therapy regimen. One-way sensitivity and probabilistic sensitivity analysis were implemented to explore the uncertainty and validate the stability of results.

 

Results

In the base-case, the ICUR of sacituzumab govitecan versus chemotherapy is $ 778,771.9/QALY and $ 702,281/QALY for full population group and brain metastatic-negative (BMN) group with the setting of classic survival mode. And in the setting of cure survival mode, the ICUR is $ 506,504.5/QALY for the full population group and $ 274,232.0/QALY for BMN population group. One-way sensitivity analyses revealed that the unit cost of sacituzumab govitecan and body weight were key roles that lower the ICUR value. Probabilistic sensitivity analyses also showed that reducing the unit price of sacituzumab govitecan can improve the likelihood of becoming cost-effective.

 

Conclusion

The cost-effectiveness analysis suggested that from a US payer perspective, sacituzumab govitecan at current price is unlikely to be a preferred option for patients with advanced or metastatic TNBC at a threshold of $ 150,000/QALY.

 

 

Early breast cancer in women aged 35 years or younger: A large national multicenter French population-based case control-matched analysis

by Ondine Dufour, Gilles Houvenaeghel, Jean-Marc Classe, Monique Cohen, Christelle Faure, Chafika Mazouni, Marie-Pierre Chauvet, Eva Jouve, Emile Darai, Anne-Sophie Azuar, Pierre Gimbergues, Anthony Gonçalves, Alexandre de Nonneville 

The Breast: Published: February 08, 2023

Background

There is a scarcity of data exploring early breast cancer (eBC) in very young patients. We assessed shared and intrinsic prognostic factors in a large cohort of patients aged ≤35, compared to a control group aged 36 to 50.

Methods

Patients ≤50 were retrospectively identified from a multicentric cohort of 23,134 eBC patients who underwent primary surgery between 1990 and 2014. Multivariate Cox analyses for DFS and OS were built. To assess the independent impact of age, 1 to 3 case-control analysis was performed by matching ≤35 and 36–50 years patients.

Results

Of 6481 patients, 556 were aged ≤35, and 5925 from 36 to 50. Age ≤35 was associated with larger tumors, higher grade, ER-negativity, macroscopic lymph node involvement (pN + macro), lymphovascular invasion (LVI), mastectomy, and chemotherapy (CT) use. In multivariate analysis, age ≤35 was associated with worse DFS [HR 1.56, 95% CI 1.32–1.84; p < 0.001], and OS [HR 1.29, 95% CI 1.03–1.60; p = 0.025], as were high grade, large tumor, LVI, pN + macro, ER-negativity, period of diagnostic, and absence of ET or CT (for DFS). Adverse prognostic impact of age ≤35 was maintained in the case control-matched analysis for DFS [HR 1.56, 95%CI 1.28–1.91, p < 0.001], and OS [HR 1.33, 95%CI 1.02–1.73, p = 0.032]. When only considering patients ≤35, ER, tumor size, nodal status, and LVI were independently associated with survival in this subgroup.

Conclusions

Age ≤35 is associated with less favorable presentation and more aggressive treatment strategies. Our results support the poor prognosis value of young age, which independently persisted when adjusting for other prognostic factors and treatments.

 

Taxane rechallenge during metastatic disease in HER-2 negative breast cancer patients: Clinical activity, tolerance and survival results

by Manon Réda, Anaïs Fouquier, Isabelle Desmoulins, Didier Mayeur, Courèche Kaderbhai, Silvia Ilie, Audrey Hennequin, Bruno Coudert, Aurélie Bertaut, Sylvain Ladoire 

The Breast: Published:February 04, 2023

Background

Taxanes are major drugs for metastatic breast cancer (MBC) treatment, and are generally well tolerated, making them attractive for therapeutic reintroduction (rechallenge) during metastatic course. In view of the paucity of current literature, we questioned the usefulness of taxane rechallenge in a population of patients previously treated with taxanes in a metastatic setting.

 

Methods

From the local database of a French cancer center, we retrospectively identified 756 patients diagnosed with ER+/HER2-, or triple negative MBC, and treated between 2008 and 2021. Among them, 58 patients (7.8%) were rechallenged with taxanes. Clinical characteristics, response rates, and survival were retrospectively evaluated and compared to patients who received taxanes only once.

 

Results

Compared to non-rechallenged population, patients treated with taxane rechallenge were significantly younger, with better general status, and received more treatment. First taxane exposure led to better tumor response and was more frequently discontinued for reasons other than progression, compared to the non-rechallenged population. Taxane rechallenge led to an objective response rate of 27.6%, and a clinical benefit rate of 46.6%, with a median progression-free survival (PFS) of 5.7 months, and a median overall survival (OS) of 11.6 months. We also found a PFS2/PFS1 ratio >1.3 in 55.2% of the rechallenge population.

 

Conclusion

Although only a minority of MBC patients are concerned, taxane rechallenge appears to be a pragmatic option with an acceptable tolerance, and good efficacy, especially when these drugs have shown clinical activity earlier in the disease course, and/or have been stopped for reasons other than progression.

 

 

Cisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): a randomised, double-blind, placebo-controlled, phase 2 trial

by Eve Rodler, Priyanka Sharma, William E Barlow, Julie R Gralow, Shannon L Puhalla, Carey K Anders, Lori Goldstein, Debu Tripathy, Ursa A Brown-Glaberman, Thu-Tam Huynh, Christopher S Szyarto, Andrew K Godwin, Harsh B Pathak, Elizabeth M Swisher, Marc R Radke, Kirsten M Timms, Danika L Lew, Jieling Miao, Lajos Pusztai, Daniel F Hayes, Gabriel N Hortobagyi 

The Lancet Oncology: VOLUME 24, ISSUE 2, P162-174, FEBRUARY 2023

Background

Poly(ADP-ribose) polymerase (PARP) inhibitors are effective in germline BRCA1 or BRCA2 (BRCA1/2) mutation-associated metastatic breast cancer. However, studies evaluating PARP inhibitors plus platinum-based chemotherapy in germline BRCA1/2-wildtype triple-negative breast cancer are scarce. A large proportion of germline BRCA1/2-wildtype triple-negative breast cancer shows homologous recombination deficiency (HRD), resulting in a BRCA-like phenotype that might render sensitivity to PARP inhibitors. The S1416 trial assessed the efficacy of cisplatin combined with the PARP inhibitor veliparib in three predefined groups of metastatic breast cancer: germline BRCA1/2-mutated, BRCA-like, and non-BRCA-like.

 

Methods

S1416 was a randomised, double-blind, placebo-controlled, phase 2 trial conducted at 154 community and academic clinical sites across the USA. Eligible patients aged 18 years or older had metastatic or recurrent triple-negative breast cancer or germline BRCA1/2-associated metastatic or recurrent breast cancer, an Eastern Cooperative Oncology Group performance status of 0–2, and had received up to one line of chemotherapy for metastatic disease. Patients were randomly assigned (1:1) via the National Clinical Trials Network open interactive system with dynamic balancing on number of previous cytotoxic regimens for metastatic disease to receive intravenous cisplatin (75 mg/m2, day 1) combined with either veliparib or matching placebo (300 mg orally twice a day, days 1–14) on a 21-day cycle. Investigators, patients, and the sponsors were masked to treatment assignment; the study statisticians were unmasked. Central testing after ran domisation classified patients as having mutated or wildtype germline BRCA1/2. A biomarker panel established a priori was used to classify patients with wildtype germline BRCA1/2 into BRCA-like and non-BRCA-like phenotype groups, with BRCA-like status based on at least one of the biomarkers: genomic instability score (≥42), somatic BRCA1/2 mutations, BRCA1 promoter methylation, or non-BRCA1/2 homologous recombination repair germline mutations. The primary endpoint was investigator-assessed progression-free survival, analysed separately for the three predefined biomarker groups with a prespecified α value for each analysis. Efficacy analyses were done by intention to treat and included all eligible patients. Safety analyses of toxicities attributed to treatment included all patients who received at least one dose of veliparib or placebo. The study is ongoing and registered with ClinicalTrials.gov, NCT02595905.

 

Findings

Between July 7, 2016, and June 15, 2019, 335 patients were enrolled and randomly assigned. 320 patients (n=162 to cisplatin plus veliparib, all women; and n=158 to cisplatin plus placebo, 157 women and one man) were eligible for efficacy evaluation. 247 patients were classified into the three biomarker groups: germline BRCA1/2-mutated (n=37), BRCA-like (n=101), and non-BRCA-like (n=109). 73 patients could not be classified due to missing biomarker information. Median follow-up was 11·1 months (IQR 5·6–20·8). In the germline BRCA1/2-mutated group, median progression-free survival was 6·2 months (95% CI 2·3–9·2) in the cisplatin plus veliparib group and 6·4 months (4·3–8·2) in the cisplatin plus placebo group (HR 0·79 [95% CI 0·38–1·67]; log-rank p=0·54). In the BRCA-like group, median progression-free survival was 5·9 months (95% CI 4·3–7·8) in the cisplatin plus veliparib group versus 4·2 months (2·3–5·0) in the cisplatin plus placebo group (HR 0·57 [95% CI 0·37–0·88]; p=0·010). In the non-BRCA-like group, median progression-free survival was 4·0 months (95% CI 2·5–4·7) in the cisplatin plus veliparib group versus 3·0 months (2·2–4·4) in the cisplatin plus placebo group (HR 0·89 [95% CI 0·60–1·33]; p=0·57). The most common grade 3 or worse adverse events attributed to treatment were neutropenia (71 [46%] of 155 patients in the cisplatin plus veliparib group vs 29 [20%] of 147 in the cisplatin plus placebo group), leukopenia (42 [27%] vs 11 [7%]), anaemia (35 [23%] vs 12 [8%]), and thrombocytopenia (29 [19%] vs four [3%]). Serious adverse events attributed to treatment occurred in 48 (31%) patients in the cisplatin plus veliparib group and 53 (36%) patients in the cisplatin plus placebo group. Treatment-related adverse events led to death in one patient in the cisplatin plus veliparib group (sepsis) and one patient in the cisplatin plus placebo group (acute kidney injury due to cisplatin plus heart failure from previous doxorubicin exposure).

Interpretation

The addition of veliparib to cisplatin significantly improved progression-free survival in patients with BRCA-like metastatic triple-negative breast cancer, but not in patients with non-BRCA-like metastatic breast cancer. PARP inhibitors combined with platinum-based chemotherapy should be explored further in BRCA-like triple-negative breast cancer.

Thursday 2 February 2023

Breast Surgery Bulletin: Feb 2023

 

Factors associated with weight gain after breast cancer: Results from a community-based survey of Australian women

 

by Carolyn Ee, Adele Cave, Vaishnavi Vaddiparthi, Dhevaksha Naidoo, John Boyages 

 

The Breast: Published: January 25, 2023

 

Purpose

Weight gain after breast cancer is common. The aim of this study was to determine factors associated with weight gain after breast cancer in Australian women.

Methods

A cross-sectional online survey was conducted between November 2017 and January 2018. Women living in Australia who self-identified as having breast cancer or ductal carcinoma in-situ were eligible. We created stepwise linear and logistic regression models to evaluate predictors for absolute and clinically significant (≥5%) weight gain respectively.

Results

Data from 276 women were analysed. Most were Caucasian and 92% had been diagnosed with Stage 0-III breast cancer. Absolute weight gain was associated with hot flushes, being in the menopausal transition at diagnosis, being less physically active than at diagnosis, lower eating self-efficacy when watching television or using a computer, and higher self-efficacy when anxious or nervous (F-ratio = 3.26, R2-adjusted = 0.16, p < .001). Clinically significant weight gain was associated with tamoxifen use (OR 2.7), being less physically active than at diagnosis (OR 3.1), and lower eating self-efficacy when watching television or using a computer (OR 0.82) (Chi-square 64.94, df = 16, p < .001). Weight gain was not associated with chemotherapy, radiotherapy, aromatase inhibitor use, number of lymph nodes removed, or body mass index at diagnosis.

Conclusions

Interventions to prevent weight gain after breast cancer, particularly aiming to maintain physical activity, should be targeted at women receiving tamoxifen. The role of eating self-efficacy, especially attentive eating, in managing weight after breast cancer should be explored.