Wednesday, 30 December 2020

CDK 4/6 inhibitors mired in uncertainty in HR positive and HER2 negative early breast cancer

 

CDK 4/6 inhibitors mired in uncertainty in HR positive and HER2 negative early breast cancer

The Breast:  VOLUME  55, P75-78, FEBRUARY 01, 2021

by Serena Di Cosimo, Luca Porcu, Fatima Cardoso 

Highlights

•HR+/HER2-early BC patients have continuous risk of relapse and need new therapies

•Current short follow-up precludes any final conclusion re. adjuvant CDK4/6 inhibitors

•The proportional hazard assumption was hampered by the low number of events

•Wide point estimate 95%CI translated into imprecise number needed to treat (NNT)

•Besides efficacy, toxicity, compliance and cost are issues to consider in decision-making

•Research efforts need to continue to establish CDK4/6 inhibitor predictive biomarkers

Abstract

Cell-cycle abnormalities are common in estrogen receptor- and/or progesterone receptor-positive, and HER2-non-overexpressing (HR+/HER2-) breast cancer, and have long been considered potential therapeutic targets. Cyclin-dependent kinase (CDK) 4/6 inhibitors have dramatically changed the therapeutic management of HR+/HER2-advanced breast cancer by prolonging progression-free and overall survival when given in combination with endocrine therapy. In this article, available data from PALLAS and monarchE trials regarding the efficacy and toxicity of adjuvant combined therapy with CDK 4/6 inhibitors and endocine therapy in HR+/HER2-early breast cancer are reviewed, and relevant issues including study hypothesis, patient selection, and duration of follow-up are discussed.

Acute Postoperative Complications in Prepectoral versus Subpectoral Reconstruction following Nipple-Sparing Mastectomy

 

Acute Postoperative Complications in Prepectoral versus Subpectoral Reconstruction following Nipple-Sparing Mastectomy

 

 

by Avila, Azalia; Bartholomew, Alex J.; Sosin, Michael; Deldar, Romina; Griffith, Kayla F.; Willey, Shawna C.; Song, David H.; Fan, Kenneth L.; Tousimis, Eleni A.

 

Plastic and Reconstructive Surgery:  December 2020 - Volume 146 - Issue 6 - p 715e-720e

 

Background:

Nipple-sparing mastectomy is associated with improved aesthetics and oncologic safety. Recently, there has been a resurgence in prepectoral reconstruction. Because of limited data comparing complication rates on patients undergoing prepectoral breast reconstruction, this study compared 30-day postoperative complications by plane of prosthetic placement.

Methods:

A retrospective review was conducted on all consecutive patients undergoing nipple-sparing mastectomy with implant-based reconstruction with either prepectoral or subpectoral placement from 2014 to 2018. The primary outcome was a composite, acute 30-day postoperative complication, including nipple-areola complex necrosis, mastectomy flap necrosis, wound dehiscence, infection, hematoma, and seroma. Secondary outcomes included nipple loss and rates of unintended reoperations. Univariate and mixed effects multivariate logistic regression were used to compare outcomes.

Results:

A total of 228 patients and 405 breasts were included in the final cohort, with 202 in the subpectoral cohort and 203 in the prepectoral cohort. The overall complication rate was 7.65 percent, with no significant difference between subpectoral and prepectoral cohorts (9.41 percent versus 5.91 percent, respectively; p = 0.148). Prepectoral reconstruction was associated with significantly reduced ischemic complications, including nipple loss because of necrosis (2.97 percent versus 0.49 percent, respectively; p = 0.015) and mastectomy flap necrosis (5.45 percent versus 0 percent; p = 0.003). There were no significant differences in rates of infection, hematoma, seroma, or implant loss/exchange.

Conclusions:

Prepectoral reconstruction is associated with similar overall 30-day postoperative complications and reoperations compared to traditional subpectoral implants. However, prepectoral reconstruction was associated with significantly decreased ischemic complications, including mastectomy flap necrosis and nipple-areola complex loss because of necrosis. Clinical Question/Level of Evidence: Therapeutic, III.

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

 

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

 

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

 

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

 

Highlights

•Mammographic sensitivity is a key indicator of screening effectiveness.

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

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

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

Background

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

Methods

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

Results

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

Conclusion

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

Decisional conflict in breast cancer patients considering immediate breast reconstruction

 

Decisional conflict in breast cancer patients considering immediate breast reconstruction

 

The Breast: Published: December 09, 2020

 

by Jacqueline A. ter Stege, Hester S.A. Oldenburg, Leonie A.E. Woerdeman, Arjen J. Witkamp, Jacobien M. Kieffer, Martine A. van Huizum, Frederieke H. van Duijnhoven, Daniela E.E. Hahn, Miranda A. Gerritsma, Marianne A. Kuenen, Nicola (A.N.) Kimmings, Quinten (P.Q.) Ruhé, Irene S. Krabbe-Timmerman, Martijne van’t Riet, Eveline M.L. Corten, Kerry A. Sherman, Eveline M.A. Bleiker

Highlights

•A majority of patients considering immediate breast reconstruction experience decisional conflict.

•Patients without a strong preference for breast reconstruction are more likely to experience decisional conflict.

•Patients with more anxiety are more likely to experience decisional conflict.

Background

Breast cancer (BC) patients who are treated with mastectomy are frequently offered immediate breast reconstruction. This study aimed to assess decisional conflict in patients considering immediate breast reconstruction, and to identify factors associated with clinically significant decisional conflict (CSDC).

Methods

Baseline data of a multicenter randomized controlled trial evaluating the impact of an online decision aid for BC patients considering immediate breast reconstruction after mastectomy were analyzed. Participants completed questionnaires assessing sociodemographic and clinical characteristics, decisional conflict and other patient-reported outcomes related to decision-making such as breast reconstruction preference, knowledge, information resources used, preferred involvement in decision-making, information coping style, and anxiety. Multivariable logistic regression analysis was performed to identify factors associated with CSDC (score > 37.5 on decisional conflict).

Results

Of the 250 participants, 68% experienced CSDC. Patients with a slight preference for breast reconstruction (odds ratio (OR) = 6.19, p <.01), no preference for or against breast reconstruction (OR = 11.84, p <.01), and a strong preference for no breast reconstruction (OR = 5.20, p <.05) were more likely to experience CSDC than patients with a strong preference for breast reconstruction. Furthermore, patients with more anxiety were more likely to experience CSDC (OR = 1.03, p = .01).

Conclusion

A majority of BC patients who consider immediate breast reconstruction after mastectomy experience clinically significant decisional conflict. The findings emphasize the need for decision support, especially for patients who do not have a strong preference for breast reconstruction.

 

The Influence of Fat Grafting on Breast Imaging after Postmastectomy Reconstruction: A Matched Cohort Analysis

 

The Influence of Fat Grafting on Breast Imaging after Postmastectomy Reconstruction: A Matched Cohort Analysis

 

by Cason, Roger W.; Shammas, Ronnie L.; Broadwater, Gloria; Glener, Adam D.; Sergesketter, Amanda R.; Vernon, Rebecca; Le, Elliot; Wickenheisser, Victoria A.; Marks, Caitlin E.; Orr, Jonah; Pyfer, Bryan J.; Hollenbeck, Scott T.

 

Plastic and Reconstructive Surgery: December 2020 - Volume 146 - Issue 6 - p 1227-1236

 

Background:

Fat grafting to the reconstructed breast may result in the development of benign lesions on physical examination, prompting further investigation with imaging and biopsy. The aim of this study was to assess the influence of fat grafting on the incidence of imaging and biopsies after postmastectomy reconstruction.

Methods:

Patients who underwent autologous or implant-based reconstruction following mastectomy from 2010 to 2018 were identified. Those receiving fat grafting as part of their reconstructive course were propensity matched 1:1 to those that did not with body mass index, reconstruction timing, and reconstruction type as covariates in a multivariable logistic regression model.

Results:

A total of 186 patients were identified, yielding 93 propensity-matched pairs. Fat-grafted patients had higher incidences of palpable masses (38.0 percent versus 18.3 percent; p = 0.003) and postreconstruction imaging (47.3 percent versus 29.0 percent; p = 0.01), but no significant difference in the number of biopsies performed (11.8 percent versus 7.5 percent; p = 0.32). Imaging was predominately interpreted as normal (Breast Imaging-Reporting and Data System 1, 27.9 percent) or benign (Breast Imaging-Reporting and Data System 2, 48.8 percent), with fat necrosis being the most common finding [n = 20 (45.5 percent)]. No demographic, oncologic, reconstructive, or fat grafting–specific variables were predictive of receiving postreconstruction imaging on multivariate analysis. Fat grafting was not associated with decreased 5-year overall survival or locoregional recurrence-free survival.

Conclusions:

Fat grafting to the reconstructed breast is associated with increased incidences of palpable masses and subsequent postreconstruction imaging with benign radiographic findings. Although the procedure is oncologically safe, both patients and providers should be aware that concerning physical examination findings can be benign sequelae of fat grafting and may lead to increased imaging after breast reconstruction. Clinical Question/Level of Evidence: Therapeutic, III.

Comparing Outcomes of Robotically Assisted Latissimus Dorsi Harvest to the Traditional Open Approach in Breast Reconstruction

 

Comparing Outcomes of Robotically Assisted Latissimus Dorsi Harvest to the Traditional Open Approach in Breast Reconstruction

by Winocour, Sebastian; Tarassoli, Sam; Chu, Carrie K.; Liu, Jun; Clemens, Mark W.; Selber, Jesse C.  

Plastic and Reconstructive Surgery:  December 2020 - Volume 146 - Issue 6 - p 1221-1225

 

Background:

Robotically assisted latissimus dorsi harvest permits harvest of the latissimus dorsi muscle without a back incision, as compared to the traditional open technique. The authors hypothesized that robotic harvest has lower donor-site complication rates, decreased opioid requirements, and a shorter length of stay than the traditional open technique.

Methods:

A retrospective review was performed of all consecutive pedicled latissimus dorsi flaps for breast reconstruction between 2011 and 2015. All procedures were conducted by two surgeons who performed both robotic and open cases.

Results:

Fifty-two patients were identified; 25 underwent robotically assisted latissimus dorsi harvest and 27 underwent the open technique. Demographic data between the two groups were similar. Median length of stay for robotic harvest was shorter than that for the traditional technique (2 days versus 3 days; p = 0.031). Postoperative morphine requirement was less in the robotic compared to the traditional technique, but the difference was not significant (158 mg versus 184 mg; p = 0.826). Seroma rate was higher in the robotic group (16 percent versus 0 percent; p = 0.034). The mean duration of surgery was longer in the robotic cohort (388 minutes versus 311 minutes; p = 0.002).

Conclusions:

This study demonstrates robotically assisted latissimus dorsi harvest as an effective alternative to the traditional open technique in select patients. Advantages of robotic harvest include no back scar, a shorter length of stay, and lower opioid requirements, although the difference was not significant; disadvantages include longer operative time and a higher seroma rate. Clinical Question/Level of Evidence: Therapeutic, III.

A Systematic Review and Meta-analysis on the Effect of Neoadjuvant Chemotherapy on Complications Following Immediate Breast Reconstruction

 

A Systematic Review and Meta-analysis on the Effect of Neoadjuvant Chemotherapy on Complications Following Immediate Breast Reconstruction

The Breast: VOLUME  55, P55-62, FEBRUARY 01, 2021

by Jajini Varghese, Shireen S. Gohari, Hirah Rizki, F.R.C.S. ichael Faheem, Benjamin Langridge, Sherko Kümmel, Laura Johnson, Peter Schmid

 

Background

The impact of neoadjuvant chemotherapy (NACT) on surgical outcomes following immediate breast reconstruction (IBR) remains unclear. While it is generally considered safe practice to perform an IBR post NACT, reported complication rates in published data are highly variable with the majority of studies including fewer than 50 patients in the NACT and IBR arm. To evaluate this further, we conducted a systematic review and meta-analysis on the effect of NACT on autologous and implant based immediate breast reconstructions. We aimed to assess for differences in the post-operative course following IBR between patients who received NACT with those who did not.

Methods

PubMed, EMBASE, and Cochrane Library were searched from 1995 to Sept 2, 2020 to identify articles that assessed the impact of NACT on IBR. All included studies assessed outcomes following IBR. Only studies comparing reconstructed patients receiving NACT to a control group of women who did not receive NACT were included. Unadjusted relative risk of outcomes between patients who received or did not receive NACT were synthesized using a fixed-effect meta-analysis. The evidence was assessed using the Newcastle Ottawa Scale scores and GRADE. Primary effect measures were risk ratios (RRs) with 95% confidence intervals.

Results

A total 17 studies comprising 3249 patients were included in the meta-analyses. Overall, NACT did not increase the risk of complications after immediate breast reconstructions (risk ratio [RR]: 0.91, 95% CI 0.74 to 1.11, p = 0.34). There was a moderate, but not significant, increase in flap loss following NACT compared with controls (RR: 1.23, 95% CI 0.70 to 2.18, p = 0.47; I2 = 0%). Most notably, there was a statistically significant increase in implant/expander loss after NACT (RR: 1.54, 95% CI 1.04 to 2.29, p = 0.03; I2 = 34%). NACT was not shown to significantly increase the incidence of hematomas, seromas or wound complications, or result in a significant delay to commencing adjuvant therapy (RR: 1.59, 95% CI 0.66 to 3.87, p = 0.30).

Conclusion

Immediate breast reconstruction after NACT is a safe procedure with an acceptable post-operative complication profile. It may result in a slight increase in implant loss rates, but it does not delay commencing adjuvant therapy.

Residual Breast Tissue After Robot-Assisted Nipple Sparing Mastectomy

 

Residual Breast Tissue After Robot-Assisted Nipple Sparing Mastectomy

 

The Breast:  VOLUME  55, P25-29, FEBRUARY 01, 2021

 

by Ko Un Park, Gary H. Tozbikian, David J. Ferry RNFA, Allan Tsung, Mathew D. Chetta, Steven A. Schulz, Roman J. Skoracki

 

Highlights

•Robot-assisted nipple sparing mastectomy (RNSM) is technically feasible.

•Residual breast tissue after RNSM is histologically detected only from the periareolar location.

•Further clinical trials are underway to determine oncologic safety of RNSM.

Introduction

While the long-term oncologic safety of robot-assisted nipple sparing mastectomy (RNSM) remains to be elucidated, histologically detected residual breast tissue (RBT) can be a surrogate for oncologically sound mastectomy. The objective of this study is to determine the presence of RBT after RNSM.

Methods

Between August 2019–January 2020, we completed 5 cadaveric RNSMs. Full thickness biopsies from the mastectomy skin flap were obtained from predefined locations radially around the mastectomy skin envelop and nipple areolar complex to histologically evaluate for RBT.

Results

The first case was not technically feasible due to inability to obtain adequate insufflation. Five mastectomy flaps were analyzable. The average mastectomy flap thickness was 2.3 mm (range 2–3 mm) and the average specimen weight was 382.72 g (range 146.9–558.3 g). Of 70 total biopsies, RBT was detected in 11 (15.7%) biopsies. Most common location for RBT was in the nipple-areolar complex, with no RBT detected from the peripheral skin flaps.

Conclusions

In this cadaveric study, RNSM is feasible leaving minimal RBT on the mastectomy flap. The most common location for RBT is in the periareolar location consistent with previous published findings after open NSM. Clinical studies are underway to evaluate the safety of RNSM.

Hypofractionated versus conventional fractionated radiotherapy for breast cancer in patients with reconstructed breast: toxicity analysis

 Hypofractionated versus conventional fractionated radiotherapy for breast cancer in patients with reconstructed breast: toxicity analysis

The Breast: VOLUME  55, P37-44, FEBRUARY 01, 2021

by Dong-Yun Kim, Eonju Park, Chan Yeong Heo, Ung Sik Jin, Eun Kyu Kim, Wonshik Han, Kyung Hwan Shin, In Ah Kim

Highlights

•There was no significant difference in the occurrence of breast complications between the two fractionation regimens.

•Hypofractionated RT may be used comparable to conventional fractionated RT in reconstructed breast cancer patients.

•The prospective randomized trial would be necessary to clarify this issue.

Purpose

This study investigated whether hypofractionated adjuvant radiotherapy (RT) increased breast-related complication(s) compared to conventional fractionated RT in reconstructed breast cancer patients.

Methods

We conducted a retrospective review including 349 breast cancer patients who underwent immediate breast reconstruction following mastectomy or breast-conserving surgery (BCS) between 2009 and 2018 at two institutions. All patients were treated with adjuvant RT via either a conventional fractionated or hypofractionated regimen. We defined a major breast complication as a breast-related toxic event requiring re-operation or re-hospitalization during the follow-up period after the end of RT.

Results

The median follow-up was 32.3 months (4.8–118.5 months); 126 patients had conventional fractionated RT, and 223 patients received hypofractionated RT. In patients with mastectomy, there was no significant difference in the occurrence of any or major breast-related complications between the two fractionation regimens. In patients undergoing BCS, incidence of any breast complication showed no difference between two RT groups and no major breast complication was reported as well. Hypofractionated RT did not increase major wound problem (infection and dehiscence) compared to conventional RT. Incidence of major contracture was significantly lower in hypofractionated RT.

Conclusions

There was no significant difference in the occurrence of any or major breast-related complications between the two different fractionation regimens, even in patients with mastectomy. Hypofractionated RT may be used comparable to conventional fractionated RT in terms of breast-related complications in reconstructed breast cancer patients. The prospective randomized trial would be necessary to clarify this issue.

Impact of Body Mass Index on Overall Survival in patients with metastatic breast cancer Body Mass Index in metastatic breast cancer

 

Impact of Body Mass Index on Overall Survival in patients with metastatic breast cancer Body Mass Index in metastatic breast cancer

 

The Breast: VOLUME  55, P16-24, FEBRUARY 01, 2021

 

Highlights

•This is the first large multicenter cohort reporting BMI’s effect on outcomes among patients with metastatic breast cancer.

•Overweight or obese status does not negatively influence outcome of metastatic breast cancer patients, whatever the subtype.

•Underweight is a strong negative independent prognostic factor on outcomes, whatever the subtype.

Background

High Body mass index (BMI) is a risk factor for breast cancer among postmenopausal women and an adverse prognostic factor in early-stage. Little is known about its impact on clinical outcomes in patients with metastatic breast cancer (MBC).

Methods

The National ESME-MBC observational cohort includes all consecutive patients newly diagnosed with MBC between Jan 2008 and Dec 2016 in the 18 French comprehensive cancer centers.

Results

Of 22 463 patients in ESME-MBC, 12 999 women had BMI data available at MBC diagnosis. Median BMI was 24.9 kg/m2 (range 12.1–66.5); 20% of women were obese and 5% underweight. Obesity was associated with more de novo MBC, while underweight patients had more aggressive cancer features. Median overall survival (OS) of the BMI cohort was 47.4 months (95% CI [46.2–48.5]) (median follow-up: 48.6 months). Underweight was independently associated with a worse OS (median OS 33 months; HR 1.14, 95%CI, 1.02–1.27) and first line progression-free survival (HR, 1.11; 95%CI, 1.01; 1.22), while overweight or obesity had no effect.

Conclusion

Overweight and obesity are not associated with poorer outcomes in women with metastatic disease, while underweight appears as an independent adverse prognostic factor.

Tuesday, 24 November 2020

Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer

 

Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer

by B. Porte, M. Carton, F. Lerebours, E. Brain, D. Loirat, L. Haroun, A. Bellesoeur, S. Bach Hamba, Y. Kirova, P. Cottu

The Breast: Open Access, November 13, 2020

Highlights

• Efficacy and safety of palbociclib in the treatment of advanced breast cancer in real-life are very close to those from the pivotal trials.

• In the endocrine naive and endocrine sensitive population, we have highlighted three poor prognostic factors ECOG performance status 2, previous endocrine therapy for advanced breast cancer and three metastatic sites or more.

ABSTRACT

Background Palbociclib is indicated for the treatment of hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC), in combination with endocrine therapy. Emerging real-life data suggest that the efficacy of a palbociclib-based therapy is highly conserved. We report the Institut Curie hospital experience.Patients and methods We retrospectively reviewed all patients with HR+ HER2- ABC treated with a palbociclib-based therapy as first or second line for ABC, with an initial prescription from November 2016 to December 2018. Clinical, laboratory and imaging data were retrieved from electronic records. Data lock was December 31st, 2019. Descriptive analyses, univariate and multivariate Cox regression analyses were performed. Results We included 310 consecutive patients. Median age was 61.8 years old. Palbociclib was prescribed in first line in 225 patients (72.6%). Before palbociclib-based therapy initiation, 122 patients (39.3%) were endocrine naive, 96 (31.0%) endocrine sensitive and 92 (29.7%) endocrine resistant. Median follow-up was 20.7 months. Median progression free survival (PFS) was 23.4 months (95%CI: 21.6-NR) in endocrine naive patients, 22.7 months (95%CI: 14.7-NR) in endocrine sensitive, and 13.4 months (95%CI: 10.7-20.8) in endocrine resistant. At 12 months from the initiation of palbociclib, 94.5% of patients were alive. By multivariate analysis, poor prognosis factors for PFS were identified in the endocrine naive/sensitive population: initial ECOG status 2, previous endocrine therapy for ABC, 3 metastatic sites or more. Toxicity profile was similar to previously published data.Conclusion In a non-selected population of patients with HR+ HER2- ABC, the efficacy and safety data are strikingly similar to those previously reported.

Palbociclib combined with endocrine therapy in heavily pretreated HR+/HER2- advanced breast cancer patients: results from the Compassionate Use Program in Spain (PALBOCOMP)

 

Palbociclib combined with endocrine therapy in heavily pretreated HR+/HER2- advanced breast cancer patients: results from the Compassionate Use Program in Spain (PALBOCOMP)

 

The Breast:  VOLUME 54, P286-292, DECEMBER 01, 2020

 

Highlights

• CDK4/6 inhibitors combined with endocrine therapy have been widely accepted as a new standard therapy for hormone receptor-positive metastatic breast cancer patients in first or second line.

• Palbociclib alone or in combination with aromatase inhibitors, fulvestrant, or tamoxifen was effective and safe in heavily pretreated HR+/HER2- metastatic breast cancer patients.

• Palbociclib could be of higher benefit to patients with endocrine-sensitive disease that had a long duration of response to previous endocrine therapy.

• Real-world evidence of effectiveness and safety of use of palbociclib in heavily pretreated advanced breast cancer patients complements data from randomized clinical trials.

Abstract

Background

This study evaluated efficacy and safety of palbociclib, a CDK4/6 inhibitor, in heavily-pretreated hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) patients during the compassionate use program in Spain from February 2015 to November 2017.

Patients and methods

Patient data were collected retrospectively from 35 hospitals in Spain. Patients with HR+/HER2- mBC who had progressed on ≥4 treatments for advanced disease were eligible.

Results

A total of 219 patients received palbociclib in combination with aromatase inhibitors (110; 50.2%), fulvestrant (87; 39.7%), tamoxifen (8; 3.6%) or as single agent (10; 4.6%). Mean age of the patients was 58 years; 31 patients (16.1%) were premenopausal and 162 (83.9%) were postmenopausal at the beginning of treatment with palbociclib. Patients had received a median of 3 previous lines of endocrine therapy (ET) for advanced disease. Real-world tumor response (rwTR) and clinical benefit rate were 5.9% (n = 13) and 46.2% (n = 101), respectively. The median real world progression-free survival (rwPFS) was 6.0 months (95% CI 5.7–7.0) and the median overall survival was 19.0 months (95% CI 16.4–21.7). Subgroup analysis revealed a significant difference in median rwPFS in patients treated with palbociclib plus fulvestrant depending on the duration of prior treatment with fulvestrant monotherapy (>6 versus ≤6 months; HR 1.93, 95% CI 1.37–2.73, p < 0.001). The most frequently reported toxicities were neutropenia, asthenia, thrombopenia and anemia.

Conclusions

Palbociclib can be an effective and safe treatment option in patients with heavily pretreated endocrine-sensitive mBC, especially in those with longer PFS to previous ET.

Peripheral cytotoxic T lymphocyte predicts first-line progression free survival in HER2-positive advanced breast cancer

 

Peripheral cytotoxic T lymphocyte predicts first-line progression free survival in HER2-positive advanced breast cancer

 

by Xiao-Ran Liu, Jian-Jun Yu, Guo-Hong Song, Li-Jun Di, Han-Fang Jiang, Ying Yan, Xu Liang, Ru-Yan Zhang, Ran Ran, Jing Wang, Han Bai, Shi-Dong Jia, Hui-Ping Li

 

The Breast: Open Access, November 11, 2020

 

Highlights

•High pCTL level predicts shorter first-line PFS in HER2-positive patients receiving anti-HER2 based regimens.

•The predictive role of pCTL level found in HER2-positive patients was not applicable in hormone-positive and triple-negative breast cancer patients.

•High level of pCTL was associated with immunosuppressive status and FGFR1 mutations in HER2-positive breast cancer patients.

Abstract 

Background

The role of peripheral blood lymphocyte (pBL) in breast cancer has long been studied. However, the predictive role of pBL in advanced breast cancer (ABC) is poorly understood.

Methods

A total of 303 patients with ABC were consecutively recruited at our center between January 2015 and September 2019. At baseline, pBL subtypes were detected in all patients with 229 blood samples available for circulating tumor DNA (ctDNA) detection. pBL was analyzed through flow cytometry. ctDNA-based gene mutations were detected using next generation sequencing. The cutoff value of pCTL was estimated by X-tile software. Progression free survival (PFS) was estimated by Kaplan-Meier curve and Cox hazard proportion regression model, with difference detection by log-rank test.

Results

Median follow-up time of the study was 21.0 months. The median age of diagnosis was 52.0 years. Among the pBL subtypes, only pCTL level was found predictive for PFS in the HER2+ patients whom received anti-HER2 therapy (13.1 vs. 5.6 months, P = 0.001). However, the predictive role of pCTL was not found in HR-positive (P = 0.716) and TNBC (P = 0.202). pCTL high associated with suppressive immune indictors including lower CD4/CD8 ratio (P = 0.004) and high level of Treg cell (P = 0.004). High occurrence of FGFR1 amplification which has been reported as immune suppressor was also found in HER2+ patients with pCTL high (22.2% vs. 4.3%, P = 0.048).

Conclusions

Higher pCTLs level associated with shorter PFS and FGFR1 mutation in HER2+ ABC patients.

Breast ultrasound in breast cancer surveillance; incremental cancers found at what cost?

 

Breast ultrasound in breast cancer surveillance; incremental cancers found at what cost?

 

by Dr. Luke Bromley, Dr. Jennifer Xu, Mr. Su-Wen Loh, Dr. Grace Chew, Eddie Lau, Dr. Belinda Yeo 

 

The Breast: VOLUME 54, P272-277, DECEMBER 01, 2020

 

Highlights

• Breast ultrasound in asymptomatic surveillance after breast cancer surgery was found to have a sensitivity of 44.1%.

• Breast ultrasound detected 7 recurrences in 390 patients who did not meet criteria for adjunct breast US and had normal mammography

• Breast ultrasound generated 26 additional biopsies per 1000 US compared to mammography in surveillance, creating considerablecosts.

• Cancer detection by breast US alone did not lead to statistically significant survival benefit over mammography.

Abstract

Purpose

To determine the diagnostic parameters of breast ultrasound (US) in the setting of routine radiological surveillance after a diagnosis of breast cancer and evaluate costs of the inclusion of breast US as well as any survival benefit of US detected cases of recurrence in surveillance.

Methods

622 patients underwent breast cancer surgery and follow up at Austin Health from July 2009 to December 2015. Retrospective data analysis was performed to determine; diagnostic parameters, financial costs of US and survival outcomes of US detected cases of recurrence.

Results

Patients underwent 1–9 years of breast cancer surveillance, with a median of 4.24 years. 390 (62.7%) patients underwent additional breast US surveillance to mammography. 232 (38.3%) fit criteria for use of additional breast US. 199 abnormal imaging episodes occurred, leading to 16 screen detected-cases of locoregional recurrence. US alone generated 107 abnormal images and found 9 cancers. US had a sensitivity of 44.1%, specificity of 95.2% and positive predictive value of 11.7% in comparison to mammography; 20.6%, 97.4% and 9.9% respectively. US had a biopsy rate of 4.0% and lead to an incremental cancer detection rate of 0.38%. The cost of incremental cancer found was $31,463.72 AUD. Survival outcomes based on method of detection of recurrence were insignificant (p value = 0.71).

Conclusions

Breast US has a sensitivity of 44.1% and detected seven recurrences that were mammographically occult. Breast US has a similar PPV to mammography in surveillance. Breast US generated considerable biopsy rates and costs. Survival analysis was not able to detect any benefit of US detected cases of recurrence.

Individualized-thresholding Shear Wave Elastography Combined with Clinical Factors Improves Specificity in Discriminating Breast Masses

 Individualized-thresholding Shear Wave Elastography Combined with Clinical Factors Improves Specificity in Discriminating Breast Masses

 

by Juanjuan Gu, Eric C. Polley, Redouane Ternifi, Rohit Nayak, Judy C. Boughey, Robert T. Fazzio, Mostafa Fatemi, Azra Alizad

 

The Breast:  VOLUME 54, P248-255, DECEMBER 01, 2020

 

Highlights

•Larger mass size and lower mass depth increase false positives in breast SWE.

•Smaller mass size and increased mass depth increase false negatives in breast SWE.

•Individualized elasticity cutoffs based on lesion size and depth improves the specificity.

•Multifactorial analysis including age, individualized cutoffs, BIRADS improves sensitivity/specificity.

•Mammographic breast density does not affect the SWE measurements of breast masses.

Abstract

Purpose

To investigate the diagnostic role of new metrics, defined as individualized-thresholding of Shear Wave Elastography (SWE) parameters, in association with clinical factors (such as age, mammographic density, lesion size and depth) and the BI-RADS features in differentiating benign from malignant breast lesions.

Methods

Of 644 consecutive patients (median age, 55 years), prospectively referred for evaluation, 659 ultrasound detected breast lesions underwent SWE measurements. Multivariable logistic regression analysis was used to estimate the probability of malignancy. The area under the curve (AUC), optimal cutoff value, and the corresponding sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were determined.

Results

265 of 659 (40.2%) masses were malignant. Using two Emean cutoffs, 69.6 kPa for large superficial lesions (size >10 mm, depth ≤5 mm) and 39.2 kPa for the rest, the overall specificity, sensitivity, PPV and NPV were 92.6%, 86.8%, 88.8% and 91.3%, respectively. Combining multiple factors, including Emean with two cutoffs, age and BI-RADS, the new ROC curve based on the malignancy probability calculation showed the highest AUC (0.954, 95% CI: 0.938–0.969). Using the optimal probability threshold of 0.514, the corresponding specificity, sensitivity, PPV and NPV were 92.9%, 89.1%, 89.4% and 92.7%, respectively.

Conclusions

The false-positive rate can be significantly reduced when applying two Emean cutoffs based on lesion size and depth. Moreover, the combination of age, Emean with two cutoffs and BI-RADS can further reduce the false negatives and false positives. Overall, this multifactorial analysis improves the specificity of ultrasound while maintaining a high sensitivity.

Neoumbilicus after Selective Excision in Deep Inferior Epigastric Perforator Flap Breast Reconstruction

 Neoumbilicus after Selective Excision in Deep Inferior Epigastric Perforator Flap Breast Reconstruction

 

by Haddock, Nicholas T.; Kelling, Joseph A.; Teotia, Sumeet S. 

 

Plastic and Reconstructive Surgery: November 2020 - Volume 146 - Issue 5 - p 548e-551e

 

Summary:

The umbilicus offers no functional importance to the adult human but remains a key aesthetic landmark of the anterior abdominal wall, and its absence can be a cause for concern in aesthetic and reconstructive patients. Umbilical reconstruction or transposition for abdominoplasty and abdominally based flap operations is frequently complicated by umbilical death, infections, development of wounds needing prolonged wound care, and generally poor aesthetic outcomes. A multitude of techniques have been described to create the “ideal” neoumbilicus, but none has proven to be superior to the technique that comes before it. Our data demonstrate that, in a select set of patients, it may be beneficial to electively remove the umbilicus. Thus, umbilical reconstruction can be performed as an adjunct procedure to the primary operation with a superior aesthetic result and minimal risk for complications. This article describes the authors’ approach to delayed neoumbilical reconstruction in patients undergoing elective umbilical resection.

 

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Neoadjuvant chemotherapy and HER2 dual blockade including biosimilar trastuzumab (SB3) for HER2-positive early breast cancer: population based real world data from the Danish Breast Cancer Group (DBCG)

 

Neoadjuvant chemotherapy and HER2 dual blockade including biosimilar trastuzumab (SB3) for HER2-positive early breast cancer: population based real world data from the Danish Breast Cancer Group (DBCG)

 

by Tobias Berg, Maj-Britt Jensen, Erik H. Jakobsen, Sami Al-Rawi, Julia Kenholm, Michael Andersson 

 

The Breast: VOLUME 54, P242-247, DECEMBER 01, 2020

 

Highlights

•Real world data on 215 patients with HER2-positive early breast cancer.

•SB3 (biosimilar trastuzumab) and pertuzumab with neoadjuvant chemotherapy.

•pCR in 56% and node conversion in 68% of the patients.

•pCR rate associated with ER-status and malignancy grade.

Abstract

Background

Dual blockade with trastuzumab and pertuzumab combined with neoadjuvant chemotherapy (NACT) has been increasingly used for HER2-positive tumours >2 cm and/or with positive axillary lymph nodes in order to evaluate pathologic response and obtain better surgical management. SB3 is a registered biosimilar trastuzumab approved following a phase III trial demonstrating similar efficacy in the neoadjuvant setting as trastuzumab. However, the study was done without pertuzumab.

Method

The database of the Danish Breast Cancer Group was used to extract data on all patients who started NACT with SB3 and pertuzumab between September 1, 2018 and August 31, 2019. The primary endpoint was pathological complete response (pCR) rate.

Results

In total 215 patients received NACT and dual blockade. The median age was 55 (24–81). NACT used was cyclophosphamide and epirubicin followed by weekly paclitaxel (62% on six cycles, 35% on eight cycles) or other chemotherapy followed by weekly paclitaxel (3%). Overall, 56% of patients achieved pCR. 60 of 88 node-positive patients pre-NACT achieved ypN0(i-) after neoadjuvant treatment. pCR rate was significantly associated with estrogen receptor status and malignancy grade. An association with CEP17/HER2-ratio was assessed.

Conclusion

Real world data on dual blockade with SB3 and pertuzumab in combination with NACT in a nationwide population-based study show a pCR rate comparable to that seen in previous clinical studies.

Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): an open-label, multicentre, parallel-group, randomised, phase 3 trial

 

 Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): an open-label, multicentre, parallel-group, randomised, phase 3 trial

by Ian Smith, John Robertson, Lucy Kilburn, Maggie Wilcox, Abigail Evans, Chris Holcombe, Kieran Horgan, Cliona Kirwan, Elizabeth Mallon, Mark Sibbering, Anthony Skene, Raghavan Vidya, Maggie Cheang, Jane Banerji, James Morden, Kally Sidhu, Andrew Dodson, Judith M Bliss, Mitch Dowsett

The Lancet Oncology: ARTICLES| VOLUME 21, ISSUE 11, P1443-1454, NOVEMBER 01, 2020

Background

Preoperative and perioperative aromatase inhibitor (POAI) therapy has the potential to improve outcomes in women with operable oestrogen receptor-positive primary breast cancer. It has also been suggested that tumour Ki67 values after 2 weeks (Ki672W) of POAI predicts individual patient outcome better than baseline Ki67 (Ki67B). The POETIC trial aimed to test these two hypotheses.

Methods

POETIC was an open-label, multicentre, parallel-group, randomised, phase 3 trial (done in 130 UK hospitals) in which postmenopausal women aged at least 50 years with WHO performance status 0–1 and hormone receptor-positive, operable breast cancer were randomly assigned (2:1) to POAI (letrozole 2·5 mg per day orally or anastrozole 1 mg per day orally) for 14 days before and following surgery or no POAI (control). Adjuvant treatment was given as per UK standard local practice. Randomisation was done centrally by computer-generated permuted block method (variable block size of six or nine) and was stratified by hospital. Treatment allocation was not masked. The primary endpoint was time to recurrence. A key second objective explored association between Ki67 (dichotomised at 10%) and disease outcomes. The primary analysis for clinical endpoints was by modified intention to treat (excluding patients who withdrew consent). For Ki67 biomarker association and endpoint analysis, the evaluable population included all randomly assigned patients who had paired Ki67 values available. This study is registered with ClinicalTrials.govNCT02338310; the European Clinical Trials database, EudraCT2007-003877-21; and the ISRCTN registry, ISRCTN63882543. Recruitment is complete and long-term follow-up is ongoing.

Findings

Between Oct 13, 2008, and April 16, 2014, 4480 women were recruited and randomly assigned to POAI (n=2976) or control (n=1504). On Feb 6, 2018, median follow-up was 62·9 months (IQR 58·1–74·1). 434 (10%) of 4480 women had a breast cancer recurrence (280 [9%] POAI; 154 [10%] control), hazard ratio 0·92 (95% CI 0·75–1·12); p=0·40 with the proportion free from breast cancer recurrence at 5 years of 91·0% (95% CI 89·9–92·0) for patients in the POAI group and 90·4% (88·7–91·9) in the control group. Within the POAI-treated HER2-negative subpopulation, 5-year recurrence risk in women with low Ki67B and Ki672W (low–low) was 4·3% (95% CI 2·9–6·3), 8·4% (6·8–10·5) with high Ki67B and low Ki672W (high–low) and 21·5% (17·1–27·0) with high Ki67B and Ki672W (high–high). Within the POAI-treated HER2-positive subpopulation, 5-year recurrence risk in the low–low group was 10·1% (95% CI 3·2–31·3), 7·7% (3·4–17·5) in the high–low group, and 15·7% (10·1–24·4) in the high–high group. The most commonly reported grade 3 adverse events were hot flushes (20 [1%] of 2801 patients in the POAI group vs six [<1%] of 1400 in the control group) and musculoskeletal pain (29 [1%] vs 13 [1%]). No treatment-related deaths were reported.

Interpretation

POAI has not been shown to improve treatment outcome, but can be used without detriment to help select appropriate adjuvant therapy based on tumour Ki67. Most patients with low Ki67B or low POAI-induced Ki672W do well with adjuvant standard endocrine therapy (giving consideration to clinical–pathological factors), whereas those whose POAI-induced Ki672W remains high might benefit from further adjuvant treatment or trials of new therapies.

Funding

Cancer Research UK.

A multivariable prognostic score to guide systemic therapy in early-stage HER2-positive breast cancer: a retrospective study with an external evaluation

 A multivariable prognostic score to guide systemic therapy in early-stage HER2-positive breast cancer: a retrospective study with an external evaluation

The Lancet Oncology : ARTICLES| VOLUME 21, ISSUE 11, P1455-1464, NOVEMBER 01, 2020

Background

In early-stage HER2-positive breast cancer, escalation or de-escalation of systemic therapy is a controversial topic. As an aid to treatment decisions, we aimed to develop a prognostic assay that integrates multiple data types for predicting survival outcome in patients with newly diagnosed HER2-positive breast cancer.

Methods

We derived a combined prognostic model using retrospective clinical–pathological data on stromal tumour-infiltrating lymphocytes, PAM50 subtypes, and expression of 55 genes obtained from patients who participated in the Short-HER phase 3 trial. The trial enrolled patients with newly diagnosed, node-positive, HER2-positive breast cancer or, if node negative, with at least one risk factor (ie, tumour size >2 cm, histological grade 3, lymphovascular invasion, Ki67 >20%, age ≤35 years, or hormone receptor negativity), and randomly assigned them to adjuvant anthracycline plus taxane-based combinations with either 9 weeks or 1 year of trastuzumab. Trastuzumab was administered intravenously every 3 weeks (8 mg/kg loading dose at first cycle, and 6 mg/kg thereafter) for 18 doses or weekly (4 mg/kg loading dose in the first week, and 2 mg/kg thereafter) for 9 weeks, starting concomitantly with the first taxane dose. Median follow-up was 91·4 months (IQR 75·1–105·6). The primary objective of our study was to derive and evaluate a combined prognostic score associated with distant metastasis-free survival (the time between randomisation and distant recurrence or death before recurrence), an exploratory endpoint in Short-HER. Patient samples in the training dataset were split into a training set (n=290) and a testing set (n=145), balancing for event and treatment group. The training set was further stratified into 100 iterations of Monte-Carlo cross validation (MCCV). Cox proportional hazard models were fit to MCCV training samples using Elastic-Net. A maximum of 92 features were assessed. The final prognostic model was evaluated in an independent combined dataset of 267 patients with early-stage HER2-positive breast cancer treated with different neoadjuvant and adjuvant anti-HER2-based combinations and from four other studies (PAMELA, CHER-LOB, Hospital Clinic, and Padova) with disease-free survival outcome data.

Findings

From Short-HER, data from 435 (35%) of 1254 patients for tumour size (T1 vs rest), nodal status (N0 vs rest), number of tumour-infiltrating lymphocytes (continuous variable), subtype (HER2-enriched and basal-like vs rest), and 13 genes composed the final model (named HER2DX). HER2DX was significantly associated with distant metastasis-free survival as a continuous variable (p<0·0001). HER2DX median score for quartiles 1–2 was identified as the cutoff to identify low-risk patients; and the score that distinguished quartile 3 from quartile 4 was the cutoff to distinguish medium-risk and high-risk populations. The 5-year distant metastasis-free survival of the low-risk, medium-risk, and high-risk populations were 98·1% (95% CI 96·3–99·9), 88·9% (83·2–95·0), and 73·9% (66·0–82·7), respectively (low-risk vs high-risk hazard ratio [HR] 0·04, 95% CI 0·0–0·1, p<0·0001). In the evaluation cohort, HER2DX was significantly associated with disease-free survival as a continuous variable (HR 2·77, 95% CI 1·4–5·6, p=0·0040) and as group categories (low-risk vs high-risk HR 0·27, 0·1–0·7, p=0·005). 5-year disease-free survival in the HER2DX low-risk group was 93·5% (89·0–98·3%) and in the high-risk group was 81·1% (71·5–92·1).

Interpretation

The HER2DX combined prognostic score identifies patients with early-stage, HER2-positive breast cancer who might be candidates for escalated or de-escalated systemic treatment. Future clinical validation of HER2DX seems warranted to establish its use in different scenarios, especially in the neoadjuvant setting.

The Baker Classification for Capsular Contracture in Breast Implant Surgery Is Unreliable as a Diagnostic Tool

 

The Baker Classification for Capsular Contracture in Breast Implant Surgery Is Unreliable as a Diagnostic Tool

 

by de Bakker, Erik; Rots, Mathijs; Buncamper, Marlon E.; Niessen, Frank B.; Smit, Jan Maerten; Winters, Henri A. H.; Özer, Müjde; de Vet, Henrica C. W.; Mullender, Margriet G.

Plastic and Reconstructive Surgery: November 2020 - Volume 146 - Issue 5 - p 956-962

 

Background:

Breast implants are frequently used in cosmetic and reconstructive breast surgery. Capsular contracture, the most common long-term complication, is usually graded using the Baker classification. Despite its widespread use, the reliability of the Baker classification has never been established. The aim of this study was to determine the interobserver reliability and agreement of the Baker classification.

Methods:

Sixty women who had undergone cosmetic breast augmentation were included. They were examined independently by two plastic surgeons from an observer pool. The Baker score was determined, along with firmness, dislocation, symmetry, and pain using four-point scales. Patients were asked to complete the BREAST-Q postaugmentation module. The interobserver reliability and agreement were calculated for all variables with a quadratic weighted kappa.

Results:

The interobserver reliability of the Baker classification was poor (kappa, 0.55; 95 percent CI, 0.37 to 0.72). Interobserver reliability of the clinical parameters firmness (0.64; 95 percent CI, 0.49 to 0.79), dislocation (0.49; 95 percent CI, 0.26 to 0.73), and symmetry (0.61; 95 percent CI, 0.34 to 0.88) was also poor. Pain scores seemed more reliable (0.72; 95 percent CI, 0.56 to 0.89); however, most patients had no pain. The interobserver agreement for the Baker score was 48 percent; in 43 percent, the observers differed one category; and in 12 percent, the difference was more than one category.

Conclusions:

Interobserver reliability and observer agreement of the Baker classification for capsular contracture were poor. Consensus about how to adequately rate the symptoms of capsular complaints is lacking. A more reliable method of measurement or description is needed, especially for scientific research purposes, to assess the long-term problems associated with breast implants. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.