Breast Surgery Bulletin - November 2021

 

Novel prognostic classification predicts overall survival of patients receiving salvage whole-brain radiotherapy for recurrent brain metastasis from breast cancer: A recursive partitioning analysis (KROG 16-12)

 

 

by Jae Sik Kim, Kyubo Kim, Wonguen Jung, Kyung Hwan Shin, Seock-Ah Im, Yong Bae Kim, Jee Suk Chang, Doo Ho Choi, Haeyoung Kim, Yeon Hee Park, Dae Yong Kim, Tae Hyun Kim, Jeanny Kwon, Ki Mun Kang, Woong-Ki Chung, Kyung Su Kim, In Ah Kim 

 

The Breast: Open Access: Published: November 15, 2021

 

 

Background

To investigate outcomes of salvage whole-brain radiotherapy (WBRT) for recurrent brain metastases (BM) from breast cancer (BC), to identify prognostic factors of overall survival (OS), and to propose a novel prognostic classification for OS in these patients.

Materials and methods

We identified 54 patients who had received salvage WBRT as the second brain-focused treatment for recurrent BM from BC (2000–2014). The median follow-up duration was 4.9 months. A recursive partitioning analysis (RPA) was conducted to develop a model to predict OS at the time of salvage WBRT.

Results

The median OS was 6.8 months. OS according to BC-specific graded prognostic assessment (breast-GPA), modified breast-GPA, and updated breast-GPA did not represent our cohort. In the multivariate analysis, a long time before salvage WBRT (≥16 months), control of primary BC or extracranial metastases, systemic treatment after salvage WBRT, and administration of a biologically effective dose for an α/β of 10 Gy (BED10) of salvage WBRT >37.5 Gy showed superior OS. We proposed three RPA classes based on the control of both primary BC and extracranial metastasis and BED10 of salvage WBRT: class I, class II, and class III. In this model, patients with class I experienced the best OS (34.6 months; class II, 5.0 months; class III, 2.4 months; P < 0.001).

Conclusions

In our RPA classification according to the control of both primary BC and extracranial metastasis and the dose of salvage WBRT, significant differences in OS were observed. The subsequent use of a systemic treatment showed better OS.

 

A Comparison of BREAST-Q Scores between Prepectoral and Subpectoral Direct-to-Implant Breast Reconstruction

 

by Le, Nicole K.; Persing, Sarah; Dinis, Jacob; Gabrick, Kyle S.; Wu, Robin T.; Sinnott, Catherine J.; Avraham, Tomer; Young, Anke Ott; Alperovich, Michael 

 

Plastic and Reconstructive Surgery: November 2021 - Volume 148 - Issue 5 - p 708e-714e

 

Background:

Subpectoral breast implant placement has in recent history predominated in breast reconstruction, but there has been more recent adoption of prepectoral implant reconstruction. There has been limited study to date of patient-reported outcomes comparing the two techniques.

Methods:

Patients who underwent direct-to-implant breast reconstruction between 2013 and 2018 were included in this retrospective cohort study. Eligible patients were asked to complete BREAST-Q domains comparing quality of life and satisfaction. Descriptive, t test, chi-square test, and multivariate linear regression analyses were performed to compare BREAST-Q scores. Significance was defined as p ≤ 0.05.

Results:

There were 64 patients (114 breasts) who underwent prepectoral reconstruction and 37 patients (68 breasts) who underwent subpectoral reconstruction. Among the 101 women (182 breasts), there were no significant differences between BREAST-Q scores and implant position for the Satisfaction with Breasts domain (adjusted p = 0.819), Psychosocial Well-being domain (adjusted p = 0.206), or Physical Well-being Chest domain (adjusted p = 0.110). The subpectoral implant cohort was associated with higher scores, 53 versus 47, for the Sexual Well-being module (adjusted p = 0.001).

Conclusions:

Patients undergoing direct-to-implant breast reconstruction had comparable BREAST-Q satisfaction scores for most modules regardless of implant plane. The subpectoral implant cohort scored higher for sexual well-being.

 

Defining Enhanced Recovery Pathway with or without Liposomal Bupivacaine in DIEP Flap Breast Reconstruction

 

by Haddock, Nicholas T.; Garza, Ricardo; Boyle, Carolyn E.; Liu, Yulun; Teotia, Sumeet S. 

 

Plastic and Reconstructive Surgery: November 2021 - Volume 148 - Issue 5 - p 948-957

 

Background:

Enhanced recovery after surgery (ERAS) includes multiple interventions that have yielded positive outcomes in a number of surgical fields. The authors evaluated whether an ERAS protocol and the subsequent addition of liposomal bupivacaine affect patient outcomes specifically in deep inferior epigastric perforator (DIEP) flap breast reconstruction.

Methods:

All patients treated with DIEP flaps from January of 2016 to December of 2019 were reviewed retrospectively. The ERAS protocol was implemented midway through 2017; halfway through 2018, intraoperative transversus abdominis plane blocks with liposomal bupivacaine were added to the protocol. Such interventions allowed for comparison of three patient groups: before ERAS, during ERAS, and after ERAS plus liposomal bupivacaine. Primary outcomes observed were postoperative opioid consumption and length of stay. The p values were obtained using the Wilcoxon test for pairwise comparisons.

Results:

After adjusting for ERAS group compliance, 216 patients were analyzed. The pre-ERAS group was composed of 67 patients, the ERAS group was composed of 69 patients, and the ERAS plus liposomal bupivacaine group was composed of 80 patients. Postoperative opioid consumption was reduced when comparing the pre-ERAS and ERAS groups (from 275.7 oral morphine equivalents to 146.7 oral morphine equivalents; p < 0.0001), and also reduced with the addition of liposomal bupivacaine (115.3 oral morphine equivalents; p = 0.016). Furthermore, hospital length of stay was decreased from 3.6 days in the pre-ERAS group to 3.2 days (p = 0.0029) in the ERAS group, and to 2.6 days (p < 0.0001) in the ERAS group plus liposomal bupivacaine groups.

Conclusions:

Enhanced recovery after surgery protocols decrease postoperative opioid consumption and hospital length of stay in DIEP flap breast reconstruction. The addition of liposomal bupivacaine further strengthens the impact of the protocol. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

 

Nomogram for the personalisation of radiotherapy treatments in breast cancer patients

by Inmaculada Beato Tortajada, Carlos Ferrer Albiach, Virginia Morillo Macias 

 

The Breast: Open Access; Published: November 08, 2021

 

Introduction

Numerous prospective studies have shown that the incorporation of genomic assays into clinical practice significantly impacts the choice of adjuvant treatments for patients with early-stage breast cancer. However, the same evidence does not exist for the treatment of locoregional recurrences.

Hypothesis and objectives

The main objective of this work was to identify the clinicopathological, molecular, and genetic parameters that allow patients to be more precisely categorised into risk groups, in order to create a locoregional recurrence riskclassification tool, the PersonalRT27.

Material and methods

To create PersonalRT27, we retrospective assessed the variables of patients with early breast cancer (stages I or II) who had undergone the OncotypeDx ® and MammaPrint ® genetic tests. These variables and factors included in the tests were categorised and weighted to obtain scores between 1 and 5 pointsto represent a lower or higher risk of relapse, respectively, based on these factors and as determined by the researchers.

Results

The mean follow-up time was 60.5 months (range 25–96 months); locoregional progression-free survival at the time of the analysis was 98.4%, and overall survival was 97.5%, of which 0.6% of the deaths had been cancer specific. The area under the curve for the PersonalRT27 was 0.76 (95% CI [0.70, 0.81]), sensitivity was 78%, and the specificity was 58.9%. We used these factors to create an inhospital web-based nomogram.

Conclusions

The PersonalRT27 is a novel tool that integrates clinical-pathological, molecular, and genetic parameters. External and independent validation will be required to implement its clinical use.

 

Interassay and interobserver comparability study of four programmed death-ligand 1 (PD-L1) immunohistochemistry assays in triple-negative breast cancer

By Aurelia Noske, Daniel-Christoph Wagner, Kristina Schwamborn, Sebastian Foersch, Katja Steiger, Marion Kiechle, Dirk Oettler, Siranush Karapetyan, Alexander Hapfelmeier, Wilfried Roth, Wilko Weichert 

 

The Breast: FULL LENGTH ARTICLE| VOLUME 60, P238-244, DECEMBER 01, 2021

 

Different immunohistochemical programmed death-ligand 1 (PD-L1) assays and scorings have been reported to yield variable results in triple-negative breast cancer (TNBC). We compared the analytical concordance and reproducibility of four clinically relevant PD-L1 assays assessing immune cell (IC) score, tumor proportion score (TPS), and combined positive score (CPS) in TNBC. Primary TNBC resection specimens (n = 104) were stained for PD-L1 using VENTANA SP142, VENTANA SP263, DAKO 22C3, and DAKO 28–8. PD-L1 expression was scored according to guidelines on virtual whole slide images by four trained readers.

The mean PD-L1 positivity at IC-score ≥1% and CPS ≥1 ranged between 53% and 75% with the highest positivity for SP263 and comparable levels for 22C3, 28–8, and SP142. Inter-assay agreement was good between 28–8 and 22C3 across all scores and cut-offs (kappa 0.68–0.74) and for both assays with SP142 at IC-score ≥1% and CPS ≥1 (kappa 0.61–0.67). The agreement between SP263 and all other assays was substantially lower for all scores. Inter-reader agreement for each assay was good to excellent for IC-score ≥1% (kappa 0.73–0.78) and CPS ≥1 (kappa 0.68–0.74), fair to good for CPS ≥10 (kappa 0.52–0.67) and TPS ≥1% (kappa 0.53–0.72). The percentage of overlapping cases in the positive/negative category was >90% between IC-score ≥1% and CPS ≥1 but below when comparing IC-score ≥1% with CPS ≥10. We demonstrate an overall good inter-reader agreement for all PD-L1 assays in TNBC along with assay specific differences in positivity and concordances, which may aid to select the right test strategy in routine diagnostics.

 

Contralateral parenchymal enhancement on MRI is associated with tumor proteasome pathway gene expression and overall survival of early ER+/HER2-breast cancer patients

 

by Max A.A. Ragusi, Tycho Bismeijer, Bas H.M. van der Velden, Claudette E. Loo, Sander Canisius, Jelle Wesseling, Lodewyk F.A. Wessels, Sjoerd G. Elias, Kenneth G.A. Gilhuijs 

 

The Breast: FULL LENGTH ARTICLE| VOLUME 60, P230-237, DECEMBER 01, 2021

 

Purpose

To assess whether contralateral parenchymal enhancement (CPE) on MRI is associated with gene expression pathways in ER+/HER2-breast cancer, and if so, whether such pathways are related to survival.

Methods

Preoperative breast MRIs were analyzed of early ER+/HER2-breast cancer patients eligible for breast-conserving surgery included in a prospective observational cohort study (MARGINS). The contralateral parenchyma was segmented and CPE was calculated as the average of the top-10% delayed enhancement. Total tumor RNA sequencing was performed and gene set enrichment analysis was used to reveal gene expression pathways associated with CPE (N = 226) and related to overall survival (OS) and invasive disease-free survival (IDFS) in multivariable survival analysis. The latter was also done for the METABRIC cohort (N = 1355).

Results

CPE was most strongly correlated with proteasome pathways (normalized enrichment statistic = 2.04, false discovery rate = .11). Patients with high CPE showed lower tumor proteasome gene expression. Proteasome gene expression had a hazard ratio (HR) of 1.40 (95% CI = 0.89, 2.16; P = .143) for OS in the MARGINS cohort and 1.53 (95% CI = 1.08, 2.14; P = .017) for IDFS, in METABRIC proteasome gene expression had an HR of 1.09 (95% CI = 1.01, 1.18; P = .020) for OS and 1.10 (95% CI = 1.02, 1.18; P = .012) for IDFS.

Conclusion

CPE was negatively correlated with tumor proteasome gene expression in early ER+/HER2-breast cancer patients. Low tumor proteasome gene expression was associated with improved survival in the METABRIC data.

 

National health system characteristics, breast cancer stage at diagnosis, and breast cancer mortality: a population-based analysis

by Catherine Duggan, Dario Trapani, André M Ilbawi, Elena Fidarova, Mathieu Laversanne, Giuseppe Curigliano, Freddie Bray, Benjamin O Anderson 

 

The Lancet Oncology: ARTICLES| VOLUME 22, ISSUE 11, P1632-1642, NOVEMBER 01, 2021

 

Countries with low breast cancer mortality rates are characterised by increased levels of coverage of essential health services and higher numbers of public cancer centres. Among countries achieving sustained mortality reductions, the majority of breast cancers are diagnosed at an early stage, reinforcing the value of clinical early diagnosis programmes for improving breast cancer outcomes.

 

Palbociclib in combination with aromatase inhibitors in patients ≥ 75 years with oestrogen receptor-positive, human epidermal growth factor receptor 2 negative advanced breast cancer: A real-world multicentre UK study

 

by Salma El Badri, Bilal Tahir, Kirsty Balachandran, Pavel Bezecny, Fiona Britton, Mark Davies, Karen Desouza, Simon Dixon, Daniel Hills, Maung Moe, Thomas Pigott, Andrew Proctor, Yatri Shah, Richard Simcock, Anna Stansfeld, Alicja Synowiec, Marianna Theodoulou, Mark Verrill, Anshu Wadhawan, Catherine Harper-Wynne, Caroline Wilson

 

The Breast: FULL LENGTH ARTICLE| VOLUME 60, P199-205, DECEMBER 01, 2021

 

Background

Breast cancer incidence increases with age and real-world data is essential to guide prescribing practices in the older population. The aim of this study was to collect large scale real-world data on tolerability and efficacy of palbociclib + AI in the first line treatment of ER+/HER2-advanced breast cancer in those aged ≥75 years.

Methods

14 cancer centres participated in this national UK retrospective study. Patients aged ≥75 years treated with palbociclib + AI in the first line setting were identified. Data included baseline demographics, disease characteristics, toxicities, dose reductions and delays, treatment response and survival data. Multivariable Cox regression was used to assess independent predictors of PFS, OS and toxicities.

Results

276 patients met the eligibility criteria. The incidence of febrile neutropenia was low (2.2%). The clinical benefit rate was 87%. 50.7% of patients had dose reductions and 59.3% had dose delays. The 12- and 24- month PFS rates were 75.9% and 64.9%, respectively. The 12- and 24- month OS rates were 85.1% and 74.0%, respectively. Multivariable analysis identified PS, Age-adjusted Charlson Comorbidity Index (ACCI) and number of metastatic sites to be independent predictors of PFS. Dose reductions and delays were not associated with adverse survival outcomes. Baseline ACCI was an independent predictor of development and severity of neutropenia.

Conclusion

Palbociclib is an effective therapy in the real-world older population and is well-tolerated with low levels of clinically significant toxicities. The use of geriatric and frailty assessments can help guide decision making in these patients.

 

Technical Refinement in Three-Dimensional Nipple-Areola Complex Tattooing of the Reconstructed Breast

 

by Ruffolo, Alexis M.; Bruce, William J.; Daugherty, Timothy H. F.; Lee, Jason; Sommer, Nicole Z.

 

Plastic and Reconstructive Surgery: October 2021 - Volume 148 - Issue 4 - p 737-746

 

Summary: Three-dimensional nipple-areola complex tattooing has previously been described as an alternative to surgical reconstruction using local flaps and grafts. This technique offers patients an option that can achieve aesthetically pleasing results without a donor site, changes in projection over time, or additional scarring. Plastic surgeons may be limited in their ability to create a realistic-appearing nipple-areola complex because of limited experience with basic tattooing techniques and unfamiliarity with the artistic principles of light and shadow required to create depth on a two-dimensional surface. Consistent results can be achieved with attention to the technical pearls discussed in this article.

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SABR in oligometastatic breast cancer: Current status and future directions

 

by Rachel Stewart, Michelle White, Jennifer Tan, Shankar Siva, Lama Karroum, Steven David 

 

The Breast: REVIEW ARTICLE| VOLUME 60, P223-229, DECEMBER 01, 2021

 

Oligometastatic breast cancer (OMBC) is a heterogeneous disease with intrinsic biological diversity. It is increasingly accepted in clinical practice that patients with OMBC could be treated with the expectation of long-term disease remission. Local ablative treatments, such as radiotherapy or surgery have a role in this setting. At present, patients that may benefit are characterised by low tumour burden, long disease-free interval and the capacity to completely ablate all sites of disease. In the future, biological or genomic classifiers may help predict which patients may benefit the most from local ablative treatments. This review provides an overview of the proposed classifications of oligometastatic disease and outlines the standard systemic treatment options of endocrine therapy, chemotherapy, and immunotherapy. The evidence for localized treatment with stereotactic ablative body radiotherapy (SABR) is presented. We discuss current active trials in oligometastatic cancer and discuss potential future directions for the use of SABR in the treatment of OMBC.