Breast Surgery Bulletin - January 2022

 

Impacts of clinicopathological factors on efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer

by Hiromichi Nakajima, Kenichi Harano, Tokiko Nakai, Shota Kusuhara, Takehiro Nakao, Chikako Funasaka, Chihiro Kondoh, Nobuaki Matsubara, Yoichi Naito, Ako Hosono, Shuichi Mitsunaga, Genichiro Ishii, Toru Mukohara 

 

The Breast: Published: January 03, 2022

 

Highlights

•T-DXd showed favorable clinical activity against HER2-positive metastatic breast cancer.

•T-DXd showed benefit in patients with heterogeneity, reduction, or loss of HER2 expression.

•Patients with liver metastasis tended to have worse outcomes.

 

Abstract

Background

The previous second-line treatment for HER2-positive metastatic breast cancer were ado-trastuzumab emtansine (T-DM1); however, its activity is decreased in tumors with heterogenous, reduced, or loss of HER2 expression. Trastuzumab deruxtecan (T-DXd) has recently been developed as a novel antibody-drug conjugate to overcome resistance to T-DM1. However, clinical evidence on its ability to overcome this resistance is limited.

Materials and methods

We retrospectively analyzed data for patients with HER2-positive metastatic breast cancer who received T-DXd at our institution from April 2020 to March 2021. We evaluated the associations between clinicopathological and molecular biomarkers and the efficacy of T-DXd.

Results

Twenty-two patients were enrolled in this study. The median progression-free survival (PFS) was 9.7 months (95% confidence interval [CI], 7.0–not reached [NR]), and the objective response rate (ORR) was 61.9%. The ORR and PFS were comparable between patients with HER2 immunohistochemistry scores of 3+ and 2+/1+ at initial diagnosis (ORR: 50.0% vs. 72.7%, p = 0.39; median PFS, 9.7 months [95%CI, 2.6–NR] vs. 8.3 months [95%CI, 7.1–NR]; hazard ratio, 1.86 [95%CI, 0.53–6.57], p = 0.34). Two patients with heterogenous HER2 expression had a partial response or long stable disease (≥6 months). Three of four patients with re-biopsy samples after anti-HER2 targeted therapy and with latest HER2 immunohistochemistry scores of 1+ experienced partial responses (75.0%) to T-DXd, but none had responded to prior T-DM1.

Conclusions

T-DXd demonstrated favorable activity in clinical practice. Moreover, T-DXd showed meaningful benefit in patients with heterogeneity, reduction, or loss of HER2 expression.

 

Neoadjuvant approach in patients with early breast cancer evaluation of the breast cancer patient (patient assessment, staging, planning)

 

by Isabel T. Rubio, Carolina Sobrido 

 

The Breast: Published: December 31, 2021

 

Abstract

Neoadjuvant treatment (NAT) has become an option in early stage (stage I-II) breast cancer (EBC). New advances in systemic and targeted therapies have increased rates of pathologic complete response increasing the number of patients undergoing NAT. Clear benefits of NAT are downstaging the tumor and the axillary nodes to de-escalate surgery and to evaluate response to treatment. Selection of patients for NAT in EBC rely in several factors that are related to patient characteristics (i.e, age and comorbidities), to tumor histology, to stage at diagnosis and to the potential changes in surgical or adjuvant treatments when NAT is administered.

Imaging and histologic confirmation is performed to assess extent of disease y to confirm diagnosis. Besides mammogram and ultrasound, functional breast imaging MRI has been incorporated to better predict treatment response and residual disease. Contrast enhanced mammogram (CEM), shear wave elastography (SWE), or Dynamic Optical Breast Imaging (DOBI) are emerging techniques under investigation for assessment of response to neoadjuvant therapy as well as for predicting response. Surgical plan should be delineated after NAT taking into account baseline characteristics, tumor response and patient desire.

In the COVID era, we have witnessed also the increasing use of NAT in patients who may be directed to surgery, unable to have it performed as surgery has been reserved for emergency cases only.

 

Immune checkpoint inhibition in the treatment of early stage triple negative breast cancer: 2021 update

 

by Lauren C. Brown, Sherene Loi 

 

The Breast: Published: December 31, 2021

 

Abstract

There is an emerging body of evidence regarding the use of immunotherapy in early-stage triple negative breast cancer (TNBC), with the recent publication of several phase III and randomised phase II studies examining the role of immune checkpoint inhibitors (ICI) in the neoadjuvant setting in combination with chemotherapy. Evidence to date suggests that the addition of PD-1/PD-L1 inhibitors results in slight increases in the rate of pathologic complete response (pCR) seen at the time of surgery, and improved event free survival (EFS) has now been reported. However, a number of questions remain such as the optimal chemotherapy backbone; whether traditional third generation chemotherapy regimens can safely be de-escalated in the presence of an ICI; and the most appropriate sequencing of treatment in order to best harness a durable immune response and if continuation of post operative ICI is needed if one achieves a pCR. A predictive biomarker is also yet to be established, given that PD-L1 protein expression does not seem discriminatory. Given that long-term clinical outcome improvements seen thus far in early stage trials do not seem to be mediated through small changes in pathological complete response rates, new approaches in early stage trial design are now needed.

 

Exercise after Breast Augmentation: A Randomized Controlled Trial

 

by Basile, Filipe V.; Oliveira, Thais S. 

 

Plastic and Reconstructive Surgery: January 2022 - Volume 149 - Issue 1 - p 18e-24e

Background: 

There are limited scientific data regarding the impact of exercise after breast augmentation surgery. Recommendations range from a few weeks to a few months of physical activity avoidance. To decide whether early exercise after breast augmentation is safe, a prospective randomized trial was designed to measure complications, scar quality, and patient-reported outcomes in this setting.

Methods: 

The present study was a randomized controlled trial to investigate the effects of early exercise (1 week after surgery) on postoperative complications, scar quality, and patient-reported outcome (BREAST-Q). All women undergoing primary breast augmentation surgery in the authors’ institution were randomized to either standard restrictions or exercise. The three primary outcomes measured were the presence of a complication and reoperation, scar quality, and patient-reported outcome.

Results: 

A total of 225 participants were included in the final analysis. No differences were found among the groups for age (p = 0.66), implant size (p = 0.56), or implant pocket (p = 0.29); complication rates did not change between the control (7.5 percent) and exercise groups (6.9 percent). When assessed 12 months after surgery, the scar quality was comparable between the groups (29.9 control and 29.6 exercise, p = 0.204). Intervention groups (exercise) performed better on the BREAST-Q Augmentation Module: Satisfaction with Outcome score (66.3 control and 83.4 exercise, p < 0.01).

Conclusions: 

Early exercise following primary breast augmentation does not increase complication or reoperation rates or cause a reduction in scar quality after 1 year. In addition, a patient-reported outcome showed improvement in the exercise groups.

 

Silent Rupture of Silicone Gel Breast Implants: High-Resolution Ultrasound Scans and Surveys of 584 Women

 

by Salzman, Marc J. 

 

Plastic and Reconstructive Surgery: January 2022 - Volume 149 - Issue 1 - p 7-14

 

Background: 

Patient compliance has been low for U.S. Food and Drug Administration–recommended magnetic resonance imaging scans to screen silicone gel breast implants for silent rupture. High-resolution ultrasound scans are a convenient, in-office alternative that may improve screening compliance; however, women’s attitudes and feelings about silent rupture and their desire for rupture screening are unknown.

Methods: 

Plastic surgeons and staff in nine private practices received 1-day training in high-resolution ultrasound scanning, then screened women with silicone gel implants implanted since 2000. Suspect scans were reviewed by a high-resolution ultrasound–experienced plastic surgeon to determine if they showed ruptures. Surgical and scan findings were correlated. To learn attitudes and feelings about silent rupture, women took surveys before and after the scan.

Results: 

Of 584 women screened, 82 (14.0 percent) had scans showing ruptures; of 1153 implants, 92 (8.0 percent) showed ruptures. Forty women with scans showing ruptures underwent surgery, of which 30 (75 percent) had their ruptures confirmed. Surveys found 99.5 percent of women want to know if they have a rupture and 95.2 percent want the ruptured implant removed. If the scan showed no rupture, women felt relieved and 95.5 percent would get future high-resolution ultrasound screening for silent rupture. If a rupture was found, women expressed various concerns and 87.8 percent would remove the ruptured implant within 12 months.

Conclusions: 

Surveys show that women with silicone gel implants have concerns and feel anxious about possible silent rupture. Based on 14 percent of women showing a ruptured implant on high-resolution ultrasound scans and 75 percent of ruptures on high-resolution ultrasound scans surgically confirmed, 10.6 percent of women in this study have a silent rupture.

 

 

 

Invisible Surgery Concept and Scenario Strategy: How to Get the Best Aesthetic Results in Oncoplastic Breast-Conserving Surgery

 

by Zhygulin, Andrii; Fedosov, Artem; Palytsia, Valentyn 

 

Plastic and Reconstructive Surgery: December 2021 - Volume 148 - Issue 6 - p 1209-1213

 

The authors believe that oncoplastic breast surgery has to achieve the best possible aesthetic results. In this article, they propose the concept of “invisible surgery.” This is a combination of certain oncoplastic techniques that allows for restoration of the original appearance of the breast without obvious scars on the breast. Further, the authors classify the techniques as follows: the “level 1 technique,” with contour approach; the “from inside” technique; the lateral parenchymal flap; the axillary subcutaneous adipofascial flap; the rotational lateral thoracic flap; regional island perforator flaps (lateral intercostal artery perforator, lateral thoracic artery perforator, anterior intercostal artery perforator, and medial intercostal artery perforator flaps); and the nipple-sparing mastectomy with immediate expander reconstruction. These techniques were combined by internal logic—one can move from one to another according to the preoperative planning and margins status during the operation. They call their approach the “scenario strategy.” The authors have performed 138 operations in 137 patients using this approach. Most of them involved the “from inside” technique and perforator flaps. The average tumor size was 2.4 cm, and the average specimen weight was 43.2 g. The total rate of complications was 14.6 percent. According to this concept, the surgery should be performed in such way that breast appearance will not change. It should be planned as one would plan a staged procedure, taking into account possible changes in the scenario during the operation to achieve the best possible aesthetic result.

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From Salvage to Prevention: A Single-Surgeon Experience with Acellular Dermal Matrix and Infection in Prepectoral Breast Reconstruction

 

by Powers, Jeremy M.; Reuter Muñoz, Katherine D.; Parkerson, Jamie; Nigro, Lauren C.; Blanchet, Nadia P.

 

Plastic and Reconstructive Surgery: December 2021 - Volume 148 - Issue 6 - p 1201-1208

 

Background: 

Increasing amounts of acellular dermal matrix are being used with the adoption of prepectoral breast reconstruction. Postoperative infection remains a challenge in breast reconstruction, and the contribution of acellular dermal matrix type, processing, and sterility assurance level to risk of complications in prepectoral reconstruction is not well studied.

Methods: 

The authors performed a retrospective review of patients who underwent immediate prepectoral breast reconstruction from February of 2017 to July of 2020. Because of an increase in the rate of infection, the drain protocol was changed and acellular dermal matrix type was switched from AlloDerm (sterility assurance level, 10−3) to DermACELL (sterility assurance level, 10−6) in January of 2019. Demographic and surgical variables were collected, in addition to details regarding development and management of infection.

Results: 

Despite higher rates of direct-to-implant reconstruction and bilateral procedures and increased implant volumes, the rate of infection was significantly lower in patients who received DermACELL instead of AlloDerm [two of 38 (5.3 percent) versus 11 of 41 (26.8 percent); p = 0.014]. Drain duration was slightly longer in the DermACELL group, consistent with the change in drain protocol. Baseline demographic and clinical characteristics remained similar between the two groups.

Conclusions: 

With increased reliance on large amounts of acellular dermal matrix for prepectoral breast reconstruction, it directly follows that the properties of acellular dermal matrix with respect to incorporation, sterility, and implant support are that much more important to consider. There have been few studies comparing different types of acellular dermal matrix in prepectoral breast reconstruction, and further research is required to determine the contribution of acellular dermal matrix type and processing techniques to development of postoperative infection.

 

 

 

Is sarcopenia a missed factor in the management of patients with metastatic breast cancer?

 

by Elise Deluche, Denis Lachatre, Mario Di Palma, Hélène Simon, Valentin Tissot, Damien Vansteene, Philippe Meingan, Alexis Mohebi, Grégory Lenczner, Francois Pigneur, Francois Goldwasser, Bruno Raynard, the SCAN Study Group 

 

The Breast:  VOLUME 61, P84-90, FEBRUARY 01, 2022 (Published:December 15, 2021)

 

Highlights

•Sarcopenia prevalence was 29.5% in metastatic breast cancer patients.

•Pre-sarcopenia was found in 41.0% of metastatic breast cancer patients.

•Anthropometric parameters or oncologist assessments do not fully assess sarcopenia.

•Sarcopenia is under-diagnosed in metastatic cancer.

•Sarcopenic patients are under-referred for nutritional management.

Abstract

Background

Sarcopenia has emerged as an important parameter to predict outcomes and treatment toxicity. However, limited data are available to assess sarcopenia prevalence in metastatic breast cancer and to evaluate its management.

Methods

The SCAN study was a cross-sectional multicenter French study that aimed to estimate sarcopenia prevalence in a real-life sample of metastatic cancer patients. Sarcopenia was identified by low muscle mass (estimated from the skeletal muscle index at the third lumbar, via computed tomography) and low muscle strength (defined by handgrip strength). Three populations were distinguished based on EWGSOP criteria: a sarcopenic group with low muscle mass AND strength, a pre-sarcopenic group with low muscle mass OR strength and a normal group with high muscle mass AND strength.

Results

Among 766 included patients, 139 patients with breast cancer and median age of 61.2 years (29.9–97.8 years) were evaluable; 29.5% were sarcopenic and 41.0% were pre-sarcopenic. Sarcopenic patients were older (P < 0.01), had a worse PS-score (P < 0.05), and a higher number of metastatic sites (P < 0.01), the majority being hepatic and bone. A moderate agreement between the oncologist's diagnosis and sarcopenia evaluation by muscle mass and strength was recognized (Cohen's kappa = 0.45). No associations were found between sarcopenia and adverse event occurrence in the 12 patients for whom these were reported. Sarcopenic patients were underdiagnosed and nutritional care and physical activity were less proposed.

Conclusion

It is necessary to evaluate sarcopenia due to its impact on patient prognosis, and its utility in guiding patient management in metastatic breast cancer.

 

 

 

 

De-escalating axillary surgery in early stage breast cancer

 

by Eliza H. Hersh, Tari A. King 

The Breast: Published: December 15, 2021

The role of axillary surgery has evolved over the last three decades from routine axillary lymph node dissection (ALND) to sentinel lymph node biopsy to omission of axillary surgery altogether in select patients. This evolution has been achieved through the design and conduct of multiple clinical trials demonstrating that ALND does not impact survival and is not necessary for local control in patients with early-stage breast cancer and limited nodal involvement. Importantly, this practice-changing shift mirrored the trend towards earlier stage at diagnosis and the recognition of the interplay between local and systemic therapies in maintaining local control. There are numerous clinical scenarios today in which axillary staging can be safely avoided, including (1) DCIS treated with lumpectomy, (2) at the time of contralateral prophylactic mastectomy, and (3) in elderly patients with early-stage, HR+/HER2-clinically node-negative (cN0) disease. Ongoing clinical trials seek to expand the cohorts in which surgical nodal staging can be omitted. These populations include a broader range of early-stage, cN0 patients undergoing upfront surgery, as seen in the SOUND, INSEMA, BOOG 2013–08, SOAPET and NAUTILUS trials. Omission of axillary surgery in cN0 patients with HER2+ or triple-negative disease treated with neoadjuvant chemotherapy is also being tested in the ASICS and EUBREAST-01 trials. Continued advances in imaging and the growing role of genomic assays in selecting patients for systemic therapy are likely to further minimize the need for axillary surgery; thereby further reducing the morbidity of local therapy for women with breast cancer.

 

Accelerating progress in early triple-negative breast cancer: A viewpoint on antibody-drug conjugates, back from St Gallen breast cancer conference 2021

 

by Dario Trapani, Giuseppe Curigliano 

 

The Breast: Published: December 13, 2021

 

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast tumors, associated with dismal prognosis. Innovative treatments have expanded the therapeutic options for selected patients with advanced disease (mTNBC). Inter alia, the new class of molecules of antibody-drug conjugates (ADCs) has rapidly positioned in the setting of mTNBC, providing significant benefits in pretreated patients. With the advent of ADCs, progresses have been marked in targeting TNBC. Tackling this ‘un-targetable’ tumor type has been the real enterprise of the last years, overcoming the original sin of classification of TNBC in a default ‘non-positive’ category, ultimately grouping together a spectrum of heterogeneous diseases. As such, ADCs have opened an ‘identity crisis’ for TNBC treatments. These molecules are composed of a backbone of monoclonal antibody (MAb), exploiting the best role they are engineered for: recognize antigens. But ADCs are linked to cytotoxic payloads, resulting in tailored delivery of highly active agents, with the intent to spare non-targeted tissues. At the end, they interpret essentially a new pharmacological delivery model to treat tumors

The implementation of ADCs has first modernized the view on MAb clinical utilization: not really only to switch-off hyperactive tumorigenic signaling; ADCs can exert anti-neoplastic activities in disregard of the biologic functions of their pharmacological receptors: antigens are linked, payloads are released, cancer cells are killed via internalized chemotherapies. Such a change in perspective implies that: (i) ADCs can exploit activity across multiple tumor types – delivering agnostically, based on antigen expressions; (ii) ADCs offer an attractive perspective for treatment personalization, based on the multiple targetable antigens that can be identified in a single patient - a possible declination of the theranostic paradigm. Agnosticity and theranosticity, however, will be reached only with an optimal trade-off between antibody specificity – to avoid off-target effects and non-specific activity related to the release of the payload in the bloodstream – and patient tolerance of the cumulative toxicities. Pursuing precision in this context will require understanding better how these new ADCs tailor the targets; perhaps, most importantly, there must be better knowledge on what is the minimal amount of membrane antigen to be expressed, to determine ADCs efficacy, and if traditional techniques like immuno-histochemistry are sensitive enough for this purpose.

 

 

 

 

 

Surgery and prophylactic surgery in hereditary breast cancer

 

by Monica Morrow 

 

The Breast Published: December 13, 2021

 

Women with hereditary breast cancer are at increased risk of second primary cancers in the ipsilateral and contralateral breast. The level of risk varies with mutation and age at first breast cancer diagnosis. These factors as well as life expectancy should be considered when selecting the surgical approach…

 

Comparing Incision Choices in Immediate Microvascular Breast Reconstruction after Nipple-Sparing Mastectomy: Unique Considerations to Optimize Outcomes

 

by Salibian, Ara A.; Bekisz, Jonathan M.; Frey, Jordan D.; Thanik, Vishal D.; Levine, Jamie P.; Karp, Nolan S.; Choi, Mihye 

 

Plastic and Reconstructive Surgery: December 2021 - Volume 148 - Issue 6 - p 1173-1185

 

Background: 

Incision planning is a critical factor in nipple-sparing mastectomy outcomes. Evidence on optimal incision patterns in patients undergoing nipple-sparing mastectomy and immediate microvascular breast reconstruction is lacking in the literature.

Methods: 

A single-institution retrospective review was performed of consecutive patients undergoing nipple-sparing mastectomy and immediate microvascular autologous reconstruction from 2007 to 2019. Outcomes—including major mastectomy flap necrosis, full nipple-areola complex necrosis, and any major ischemic complication of the skin envelope—were compared among incision types. Multivariable logistic regression identified factors associated with major ischemic complication.

Results: 

Two hundred seventy-nine reconstructions (163 patients) were identified, primarily using internal mammary recipient vessels (98.9 percent). Vertical incisions were used in 139 cases; inframammary, in 53; lateral radial, in 51; and inverted-T, in 35. Thirty-two cases (11.5 percent) had major mastectomy flap necrosis, 11 (3.9 percent) had full nipple-areola complex necrosis, and 38 (13.6 percent) had any major ischemic complication. Inframammary incisions had higher rates of major ischemic complication (25 percent) than vertical (5.8 percent; p < 0.001) and lateral radial (7.8 percent; p = 0.032) incisions. Inverted-T incisions also had higher rates of major ischemic complication (36.1 percent) than both vertical (p < 0.001) and lateral radial (p = 0.002) incisions. Inframammary incisions (OR, 4.382; p = 0.002), inverted-T incisions (OR, 3.952; p = 0.011), and mastectomy weight (OR, 1.003; p < 0.001) were independently associated with an increased risk of major ischemic complication. Inframammary incisions with major ischemic complication demonstrated significantly higher body mass index, mastectomy weight, and flap weight compared to those without.

Conclusions: 

Inframammary and inverted-T incisions are associated with a higher risk of major ischemic skin envelope complications after nipple-sparing mastectomy and immediate microvascular breast reconstruction. Radial incisions can be considered to optimize recipient vessel exposure without compromising perfusion.

 

A scoping review of interactive and personalized web-based clinical tools to support treatment decision making in breast cancer

 

by Amy Zhao, Maya Larbi, Kristen Miller, Suzanne O'Neill, Jinani Jayasekera 

 

The Breast: VOLUME 61, P43-57, FEBRUARY 01, 2022 (Published: December 05, 2021)

 

The increasing attention on personalized breast cancer care has resulted in an explosion of new interactive, tailored, web-based clinical decision tools for guiding treatment decisions in clinical practice. The goal of this study was to review, compare, and discuss the clinical implications of current tools, and highlight future directions for tools aiming to improve personalized breast cancer care. We searched PubMed, Embase, PsychInfo, Cochrane Database of Systematic Reviews, Web of Science, and Scopus to identify web-based decision tools addressing breast cancer treatment decisions. There was a total of 17 articles associated with 21 unique tools supporting decisions related to surgery, radiation therapy, hormonal therapy, bisphosphonates, HER2-targeted therapy, and chemotherapy. The quality of the tools was assessed using the International Patient Decision Aid Standard instrument. Overall, the tools considered clinical (e.g., age) and tumor characteristics (e.g., grade) to provide personalized outcomes (e.g., survival) associated with various treatment options. Fewer tools provided the adverse effects of the selected treatment. Only one tool was field-tested with patients, and none were tested with healthcare providers. Future studies need to assess the feasibility, usability, acceptability, as well as the effects of personalized web-based decision tools on communication and decision making from the patient and clinician perspectives.