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.

 

 

 

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.

 

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.

 

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.

 

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.

 

How I treat HER2-low advanced breast cancer

 

by Ilana Schlam, Sara M. Tolaney, Paolo Tarantino 

 

The Breast: Published: January 11, 2023

 

Introduction

Targeting low levels of human receptor epidermal growth factor 2 (HER2) expression has reshaped the treatment paradigm for half of the patients with advanced breast cancer. HER2-low is currently defined as a HER2 immunohistochemical expression of 1+ or 2+ without amplification by in-situ hybridization. Until recently, HER2-targeted agents were ineffective in treating patients with HER2-low disease.

Areas covered

In this narrative review, we summarize the current management of HER2-low breast cancer. We highlight the findings of the DESTINY-Breast 04 phase 3 trial, which confirmed the efficacy of trastuzumab-deruxtecan (T-DXd) for the treatment of patients with advanced, pretreated HER2-low breast cancer. We also discuss how to implement this new treatment option in treatment algorithms of hormone receptor (HR)-positive and triple-negative tumors, as well as how to optimally manage selected toxicities of T-DXd.

Expert opinion

T-DXd is currently the standard of care for patients with advanced, pretreated, HER2-low breast cancer. Based on the design of the DESTINY-Breast04 trial, the current optimal place in treatment algorithms is after the first line of chemotherapy, both in HR-positive and triple-negative breast cancer. Up to 10–15% of the patients receiving T-DXd are expected to develop interstitial lung disease, which in 1–2% of the cases can be fatal. Adequate monitoring and prompt management are required to minimize the impact of ILD and to safely implement T-DXd in clinical practice.

 

Polygenic risk scores and breast cancer risk prediction

 

by Eleanor Roberts, Sacha Howell, Gareth Evans 

 

The Breast: VOLUME 67, P71-77, FEBRUARY 2023

 

Abstract

Polygenic Risk Scores (PRS) are a major component of accurate breast cancer risk prediction and have the potential to improve screening and prevention strategies. PRS combine the risk from Single nucleotide polymorphisms (SNPs) associated with breast cancer in Genome Wide Association Studies (GWAS) and explain over 30% of breast cancer heritability. When incorporated into risk models, the more personalised risk assessment derived from PRS, help identify women at higher risk of breast cancer development and enables the implementation of stratified screening and prevention approaches. This review describes the role of PRS in breast cancer risk prediction including the development of PRS and their clinical application. We have also examined the role of PRS within more well-established risk prediction models which incorporate known classic risk factors and discuss the interaction of PRS with these factors and their capacity to predict breast cancer subtypes. Before PRS can be implemented on a population-wide scale, there are several challenges that must be addressed. Perhaps the most pressing of these is the use of PRS in women of non-White European origin, where PRS have been shown to have attenuated risk prediction both in discrimination and calibration. We discuss progress in developing and applying PRS in non-white European populations. PRS represent a significant advance in breast cancer risk prediction and their further development will undoubtedly enhance personalisation.

 

Omission of axillary sentinel lymph node biopsy in early invasive breast cancer

 

by Toralf Reimer 

 

The Breast: Published: January 09, 2023

 

Abstract

 Local treatment of the axilla in clinically node-negative (cN0) early breast cancer patients with routine sentinel lymph node biopsy (SLNB) is debated after publication of ACOSOG Z0011 data in 2010. Currently, prospective randomized surgical trials investigating the omission of SLNB in upfront breast-conserving surgery (BCS) and in the neoadjuvant setting, respectively. Several prospective randomized trials (SOUND, INSEMA, BOOG 2013–08, and NAUTILUS) with axillary observation alone versus SLNB in cN0 patients and primary BCS have primary objectives to evaluate oncologic safety when omitting SLNB. The Italian SOUND trial was the earliest to open in 2012 and has completed accrual in 2017. First oncologic outcome data are expected soon for SOUND and at the end of 2024 for INSEMA. Improvements in systemic treatments for breast cancer have increased the rates of pathologic complete response (pCR) in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to de-escalate surgery in patients who have a pCR. Two prospective single-arm trials (EUBREAST-01, ASICS) include only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) and type of surgery will be defined according to the response to NAST rather than on the classical T and N status. The ongoing trials will hopefully help us to understand whether we might take the best therapeutic decisions without the pathologic evaluation of nodal status.

 

A systematic review of the impact of the COVID-19 pandemic on breast cancer screening and diagnosis

 

by Tong Li, Brooke Nickel, Preston Ngo, Kathleen McFadden, Meagan Brennan, M Luke Marinovich, Nehmat Houssami 

 

The Breast: VOLUME 67, P78-88, FEBRUARY 2023

Background

Breast cancer care has been affected by the COVID-19 pandemic. This systematic review aims to describe the observed pandemic-related changes in clinical and health services outcomes for breast screening and diagnosis.

Methods

Seven databases (January 2020–March 2021) were searched to identify studies of breast cancer screening or diagnosis that reported observed outcomes before and related to the pandemic. Findings were presented using a descriptive and narrative approach.

Results

Seventy-four studies were included in this systematic review; all compared periods before and after (or fluctuations during) the pandemic. None were assessed as being at low risk of bias. A reduction in screening volumes during the pandemic was found with over half of studies reporting reductions of ≥49%. A majority (66%) of studies reported reductions of ≥25% in the number of breast cancer diagnoses, and there was a higher proportion of symptomatic than screen-detected cancers. The distribution of cancer stage at diagnosis during the pandemic showed lower proportions of early-stage (stage 0–1/I-II, or Tis and T1) and higher proportions of relatively more advanced cases than that in the pre-pandemic period, however population rates were generally not reported.

Conclusions

Evidence of substantial reductions in screening volume and number of diagnosed breast cancers, and higher proportions of advanced stage cancer at diagnosis were found during the pandemic. However, these findings reflect short term outcomes, and higher-quality research examining the long-term impact of the pandemic is needed.

Breast Surgery Bulletin: December 2022

 Systemic treatment with or without ablative therapies in oligometastatic breast cancer: A single institution analysis of patient outcomes

by Gauthier Glemarec, Jean Louis Lacaze, Bastien Cabarrou, Richard Aziza, Eva Jouve, Slimane Zerdoud, Eleonora De Maio, Carole Massabeau, Maxime Loo, Vincent Esteyrie, Mony Ung, Florence Dalenc, Francoise Izar, Ciprian Chira 

The Breast: Published: December 29, 2022

Purpose

Local ablative treatment (LAT) is increasingly combined with systemic therapy in oligometastatic breast cancer (OMBC), without a high-level evidence to support this strategy. We evaluated the addition of LAT to systemic treatment in terms of progression-free survival (PFS) and overall survival (OS). Secondary endpoints were local control (LC) and toxicity. We sought to identify prognostic factors associated with longer OS and PFS.

 

Methods and materials

We identified consecutive patients treated between 2014 and 2018 for synchronous or metachronous OMBC (defined as ≤ 5 metastases). LAT included stereotactic body (SBRT) and volumetric modulated arc therapy (VMAT), surgery, cryotherapy and percutaneous radiofrequency ablation (PRA). PFS and OS were calculated and Cox regression models analyzed for potential predictors of survival.

 

Results

One hundred two patients were included (no-LAT, n = 62; LAT, n = 40). Sixty-four metastases received LAT. Median follow-up was 50.4 months (95% CI [44.4; 53.4]). One patient experienced grade 3 toxicity in the LAT group. Five-year PFS and OS were 34.75% (95% CI [24.42–45.26]) and 63.21% (95% CI [50.69–73.37]) respectively. Patients receiving both LAT and systemic therapy had longer PFS and OS than those with no-LAT ([HR 0.39, p = 0.002]) and ([HR 0.31, p = 0.01]). The use of LAT, HER2-positive status and hormone-receptor positivity were associated with longer PFS and OS whereas liver metastases led to worse PFS.

 

Conclusions

LAT was associated with improved outcomes in OMBC when added to systemic treatment alone, without significantly increasing toxicity. The prognostic factors identified to extend PFS and OS may help guide clinicians in selecting patients for LAT.

 

 

Hyperbaric oxygen therapy for local late radiation toxicity in breast cancer patients: A systematic review

 

by E.L. Meier, D.R. Mink van der Molen, C.A. Lansdorp, M.C.T. Batenburg, F. van der Leij, H.M. Verkooijen, O. Boonstra, S. Hummelink, D.J.O. Ulrich 

 

The Breast: Published: December 22, 2022

 

Purpose

This systematic review aims to provide an overview of the literature on the effect of hyperbaric oxygen therapy (HBOT) on symptoms of local late radiation toxicity (LRT) in patients treated for breast cancer.

Methods

A systematic search was performed in September 2021. All studies with a sample size of ≥10 patients reporting the effect of HBOT for symptoms of LRT after radiotherapy of the breast and/or chest wall were included. The ROBINS-I tool was used for critical appraisal of methodological quality. The toxicity outcomes pain, fibrosis, lymphedema, necrosis/skin problems, arm and shoulder mobility, and breast and arm symptoms were evaluated.

Results

Nine studies concerning a total of 1308 patients were included in this review. Except for one study, sample sizes were small. Most studies had inadequate methodology with a substantial risk of bias. Post-HBOT, a significant reduction of pain was observed in 4/5 studies, of fibrosis in 1/2 studies, and of lymphedema of the breast and/or arm in 4/7 studies. Skin problems of the breast were significantly reduced in 1/2 studies, arm- and shoulder mobility significantly improved in 2/2 studies, and breast- and arm symptoms were significantly reduced in one study.

Conclusion

This systematic review indicates that HBOT might be useful for reducing symptoms of LRT in breast cancer patients, however evidence is limited. A randomized controlled trial in a larger cohort of patients including a combination of patient- and clinician-reported outcome measures would be valuable to assess the effect of HBOT on symptoms of LRT.

 

 

 

 

Survival and prognostic factors in oligometastatic breast cancer

 

by Annemiek van Ommen-Nijhof, Tessa G. Steenbruggen, Laura Capel, Michel Vergouwen, Marie-Jeanne T. Vrancken Peeters, Terry G. Wiersma, Gabe S. Sonke 

 

The Breast: Published: December 14, 2022

 

Background

Guidelines for oligometastatic breast cancer (OMBC) propagate multimodality treatment including polychemotherapy and local ablative treatment (LAT) of all lesions. The aim of this approach is prolonged disease remission, or even cure. Long-term outcomes in OMBC and factors associated with prognosis are largely unknown, due to the rarity of this condition. We report overall survival (OS), event-free survival (EFS), and prognostic factors in a large real-world cohort of patients with OMBC.

Methods

Patients with breast cancer and 1–3 distant metastatic lesions, treated in the Netherlands Cancer Institute between 1997 and 2020, were identified via text mining of medical files. We collected patient, tumor and treatment characteristics. The Kaplan-Meier method was used to calculate OS and EFS estimates, and Cox regression analyses to assess prognostic factors.

Results

The cohort included 239 patients, of whom 54% had ERpos/HER2neg, 20% HER2pos and 20% triple negative disease. Median follow-up was 88.0 months (95% confidence interval (CI) 82.9–93.1) during which 107 patients died and 139 developed disease progression/recurrence; median OS was 93.0 months (95%CI 66.2–119.8). Factors associated with OS in multivariable analysis were subtype, disease-free interval and radiologic response to first-line systemic therapy; LAT was associated with EFS, but not OS.

Conclusions

In this large real-world cohort of patients with OMBC, OS and EFS compare favorably to survival in the general MBC population. Radiologic complete response to first-line systemic therapy was associated with favorable OS and EFS, indicating the importance of early optimal systemic therapy. The value of LAT in OMBC requires further study.

 

Adjuvant trastuzumab without chemotherapy for treating early HER2-positive breast cancer in older patients: A propensity score-adjusted analysis of a prospective cohort study

 

by RESPECT study group 

The Breast: VOLUME 66, P245-254, DECEMBER 01, 2022

Purpose

To gauge the effects of treatment practices on prognosis for older patients with HER2-positive early breast cancer, particularly to determine whether adjuvant trastuzumab alone can offer benefit over no adjuvant therapy. This is a prospective cohort study which accompanies the RESPECT that is a randomized-controlled trial (RCT).

Methods

Patients who declined the RCT were treated based on the physician's discretion. We studied the 1) trastuzumab-plus-chemotherapy group, 2) trastuzumab-monotherapy group, and 3) non-trastuzumab group (no therapy or anticancer therapy without trastuzumab). The primary endpoint was disease-free survival (DFS), which was compared using the propensity-score method. Relapse-free survival (RFS) and health-related quality of life (HRQoL) were assessed.

Results

We enrolled 123 patients aged over 70 years (median: 74.5). Treatment categories were: trastuzumab-plus-chemotherapy group (n = 36, 30%), trastuzumab-monotherapy group (n = 52, 43%), and non-trastuzumab group (n = 32, 27%). The 3-year DFS was 96.7% in trastuzumab-plus-chemotherapy group, 89.2% in trastuzumab-monotherapy group, and 82.5% in non-trastuzumab group. DFS in non-trastuzumab group was lower than in trastuzumab-plus-chemotherapy and trastuzumab-monotherapy groups (propensity-adjusted hazard ratio; HR: 3.29; 95% CI: 1.15–9.39; P = 0.026). The RFS in non-trastuzumab group was lower than in trastuzumab-plus-chemotherapy and trastuzumab-monotherapy groups (propensity-adjusted HR = 7.80; 95% CI: 2.32–26.2, P < 0.0001). There were no significant intergroup differences in the proportions of patients showing HRQoL deterioration at 36 months (P = 0.717).

Conclusion

Trastuzumab-treated patients had better prognoses than patients not treated with trastuzumab without deterioration of HRQoL. Trastuzumab monotherapy could be considered for older patients who reject chemotherapy.

 

PARP-inhibitors for BRCA1/2-related advanced HER2-negative breast cancer: A meta-analysis and GRADE recommendations by the Italian Association of Medical Oncology

 

by Federica Miglietta, Michela Cinquini, Maria Vittoria Dieci, Laura Cortesi, Carmen Criscitiello, Filippo Montemurro, Lucia Del Mastro, Alberto Zambelli, Laura Biganzoli, Alessia Levaggi, Chiara Delle Piane, Caterina Marchiò, Massimo Calabrese, Lucio Fortunato, Pierfrancesco Franco, Bruno Meduri, Veronica Andrea Fittipaldo, Stefania Gori 

 

The Breast: VOLUME 66, P293-304, DECEMBER 01, 2022

 

Background

Approximately 5–10% of unselected breast cancer (BC) patients retain a hereditary predisposition related to a germline mutation in BRCA1/2 genes. The poly-ADP ribose polymerase (PARP)-inhibitors olaparib and talazoparib have been granted marketing authorization by both FDA and EMA for adults with BRCA1/2 germline mutations and HER2-negative (HER2-) advanced BC based on the results from the phase III OlympiAd and EMBRACA trials.

Methods

The panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guidelines on Breast Cancer addressed two critical clinical questions, adopting the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach and the Evidence to Decision framework (EtD), to develop recommendations on the use of PARP-inhibitors, with respect to single-agent chemotherapy, in patients with BRCA-related triple-negative (clinical question 1) and hormone receptor-positive (HR+)/HER2- (clinical question 2) advanced BC.

Results

Two studies were eligible (OlympiAd and EMBRACA). For both clinical questions, the Panel judged the benefit/harm balance probably in favor of the intervention, given the favorable impact in terms of PFS, ORR, and QoL at an acceptable cost in terms of toxicity; the overall certainty of the evidence was low. The panel's final recommendations were conditional in favor of PARP-inhibitors over single-agent chemotherapy in both HR+/HER2-and triple-negative BC. Finally, the Panel identified and discussed areas of uncertainty calling for further exploration.

Conclusions

The Panel of AIOM BC Clinical Practice Guideline provided clinical recommendations on the use of PARP-inhibitors, with respect to single-agent chemotherapy, in patients with BRCA-related HER2-advanced BC by adopting the GRADE methodology.