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.