What's new in surgical oncology breast.

It is on the backdrop of advances in tumor biology and systemic therapy for breast cancer, that progress in locoregional treatment has focused on management of the breast for invasive cancer, imaging for staging and therapeutic decision-making, and de-escalation in the management of the axilla.

De-escalation of Post-mastectomy Irradiation in Hormone Receptor-Positive Breast Cancer with One to Three Positive Nodes.

BACKGROUND: The 21-gene recurrence score (RS) is used to predict benefit from chemotherapy in hormone receptor (HR)-positive breast cancer with one to three positive lymph nodes. Prospective-retrospective studies have shown that the RS is prognostic for both systemic and locoregional recurrence in tamoxifen-treated patients. We aimed to assess whether RS could be utilized to predict a survival benefit from postmastectomy radiation therapy (PMRT). PATIENTS AND METHODS: The National Cancer Database (NCDB) was used to identify women ≤ 75 years of age with HR+, HER2-negative, T1-3, N1, M0 breast cancer who underwent mastectomy and axillary staging with available RS during the years 2010-2016. Kaplan-Meier and Cox proportional hazards models were used to identify association between treatment and overall survival (OS). Univariate and multivariate analyses were used to identify variables correlating with PMRT and OS. RESULTS: A total of 8907 patients were identified. Of the total, 3203 (36%) patients received adjuvant PMRT and 5704 (64%) did not. Across the entire cohort, 5-year OS was 97.5% for patients receiving PMRT and 96.8% for those who did not (P = 0.063). After adjusting for all covariates, in patients with RS ≤ 25, there was no statistically significant improvement in 5-year OS with the addition of adjuvant PMRT (97.5% versus 98.1% P = 0.093). Moreover, no survival benefit was seen with axillary node dissection (P = 0.58) or with the addition of chemotherapy (P = 0.312). CONCLUSIONS: In our cohort of patients with one to three positive nodes and a RS ≤ 25, omission of post-mastectomy radiation therapy had no impact on OS. Our results suggest that RS may be utilized in the individualized decision making on PMRT.

Adjuvant chemotherapy in patients with invasive lobular carcinoma and use of the 21-gene recurrence score: A National Cancer Database analysis.

BACKGROUND: Invasive lobular carcinoma (ILC) is traditionally considered less responsive to chemotherapy. Although the Oncotype recurrence score (RS) has been validated to identify high-risk patients who benefit from chemotherapy, some studies have questioned its relevance in patients with ILC. The objective of this study was to better characterize potential use of the RS in these patients. METHODS: The National Cancer Database was used to identify women with stage I through III, T1 through T3, N0 or N1, hormone receptor-positive, HER2-negative ILC or invasive ductal carcinoma (IDC) who had an available RS between 2010 and 2016. Multivariable Cox regression was used to model the effect of variables on 5-year overall survival (OS). The Kaplan-Meier method was used to estimate OS according to the RS, nodal status, and chemotherapy. RESULTS: In total, 15,763 patients with ILC and 100,070 with IDC were identified. The mean age of patients with ILC and IDC was 59.2 ± 9.1 and 57.2 ± 9.8, respectively. A lower percentage of patients with ILC versus those with IDC had a high RS, defined as >25 (6.6% vs 16.0%; P < .0001). ILC patients with a high RS who had N0 or N1 disease received approximately 10% less chemotherapy compared with similar patients who had IDC. The results indicated that the RS had statistically significant prognostic value for patients with ILC. In addition, an absolute OS advantage was correlated with the receipt of chemotherapy by patients with ILC who had a high RS with N0 or N1 disease. CONCLUSIONS: Patients with ILC who have a high RS are treated less often with chemotherapy compared with similar patients who have IDC. Nevertheless, the RS has a prognostic as well as a predictive value in ILC, with an association between OS benefit and chemotherapy receipt in patients who have ILC with a high RS, especially if they have N1 disease. LAY SUMMARY: Invasive lobular carcinoma (ILC) is a subtype of breast cancer comprising about 15% of cases. The Oncotype recurrence score (RS) is a genetic test of breast tumors that helps predict which patients might benefit from chemotherapy. Some have doubted the relevance of the RS for patients with ILC. In this study, the authors show that the RS is relevant for patients who have ILC. The RS has the potential of predicting the risk of recurrence and identifying patients with ILC who might benefit from chemotherapy.

Keynote Address at the ASBrS 2022 Annual Meeting Low-Risk Breast Cancer: When Is Local Therapy Enough?

Surgery, radiation, and chemotherapy have all been used to de-escalate the treatment of breast cancer patients. Despite its impact on local recurrence, systemic endocrine therapy (ET) has yet to be de-escalated, even though it has substantial adverse effects and a lower quality of life (QoL) over 5-10 years. The 21-gene recurrence score (RS) and MammaPrint have been used to identify subgroups of younger patients whose long-term survival is unaffected by adjuvant ET. Local treatment only, with de-escalation of long-term systemic ET for patients aged 50-69 with RS < 11, appears not to impact OS and should have an anticipated improvement in QoL.

De-escalation of Endocrine Therapy in Early Hormone Receptor-positive Breast Cancer: When Is Local Treatment Enough?

OBJECTIVE: To identify subgroups of hormone receptor-positive (HR+) breast cancer patients that might not benefit from adding endocrine therapy (ET) to their local treatment. BACKGROUND: De-escalation in breast cancer treatment has included surgery, radiation, and chemotherapy and has often focused on older patient populations. Systemic ET has yet to be de-escalated, though it carries serious side-effects, decreasing quality of life over 5 to 10 years. We hypothesize the 21-gene recurrence score (RS) could identify subgroups of younger patients whose long-term survival is unaffected by adjuvant ET. METHODS: The National Cancer Database was used to identify women aged ≥50, with HR+, HER2-negative tumors, ≤3 cm in size, N0 status, and a RS≤25, who underwent breast-conserving surgery in 2010 to 2016. Kaplan-Meier and Cox proportional hazards models were used to identify association between treatment and overall survival (OS). RESULTS: Of the 45,217 patients identified, 80.6% were 50 to 69 years old. 42,632 (94.3%) patients received ET and 2585 (5.7%) did not. The 5-year OS was 96.4% for patients receiving ET and 93.1% for those who did not (P < 0.001). After adjusting for all covariates, patients aged 50 to 69 with RS < 11 showed no statistically significant improvement in OS when adding ET to surgery, with or without radiation (P = 0.40). With RS 11 to 25, there was a significant improvement of OS with ET plus radiation (P < 0.001). CONCLUSIONS: Local treatment only, with de-escalation of long-term ET, for patients aged 50 to 69 with RS < 11, seems not to impact OS and should have an anticipated quality of life improvement. Prospective studies investigating this approach are warranted.

The 21-gene recurrence score in node-positive, hormone receptor-positive, HER2-negative breast cancer: a cautionary tale from an NCDB analysis.

PURPOSE: The 21-gene recurrence score assay (RS) has not been prospectively validated to predict adjuvant chemotherapy benefit in hormone receptor-positive (HR+), HER2-negative (HER2-), node-positive breast cancer patients. Nevertheless, de-escalation based on RS has been demonstrated and partially advocated by retrospective data. The purpose of this study was to identify subgroups of node-positive patients with low to intermediate RS who still benefit from adjuvant chemotherapy. METHODS: The National Cancer Database was used to identify 28,591 women with stage I-III, T1-T3, N1, HR+, HER2- breast cancer and a RS ≤ 25 between 2010 and 2016. Univariate and multivariate analyses were used to identify variables correlating with chemotherapy use and 5-year survival. Subgroup analysis was performed to discern patients in whom the use of adjuvant chemotherapy correlated with better survival. RESULTS: A 35% decline in chemotherapy use was observed from 2010 to 2016. Patients with younger age, higher RS, larger tumors and more positive lymph nodes, and those treated by mastectomy, axillary lymph node dissection and radiation, were more likely to receive chemotherapy. Chemotherapy use was associated with an improved 5-year survival (HR = 1.63, 95% CI 1.28-2.07). Upon subgroup analysis, this association was lost in patients > 70 years and those with a RS ≤ 11, while patients ≤ 70 with a RS of 12-25 treated with chemotherapy had an absolute 5-year survival advantage of 3.0% (HR = 1.91, 95% CI 1.42-2.57). CONCLUSION: Clinicians should be cautious when considering omission of adjuvant chemotherapy in patients ≤ 70 years, with HR+, HER2-, N1 tumors and a RS 12-25, at least until the results of the anticipated RxPONDER trial become available.

American Society of Breast Surgeons' Practice Patterns for Patients at Risk and Affected by Breast Cancer-Related Lymphedema.

BACKGROUND: In 2017, the American Society of Breast Surgeons (ASBrS) published expert panel recommendations for patients at risk for breast cancer-related lymphedema (BCRL) and those affected by BCRL. This study sought to determine BCRL practice patterns. METHODS: A survey was sent to 2975 ASBrS members. Questions evaluated members' clinical practice type, practice duration, and familiarity with BCRL recommendations. Descriptive statistics, the chi-square test, and Fisher's exact test were used. RESULTS: Of the ASBrS members surveyed, 390 (13.1%) responded. Most of the breast surgeons (58.5%, 228/390) indicated unfamiliarity with recommendations. Nearly all respondents (98.7%, 385/390) educate at-risk patients. Most (60.2%, 234/389) instruct patients to avoid venipuncture, injection or blood pressure measurements in the at-risk arm, and 35.6% (138/388) recommend prophylactic compression sleeve use during air travel. Nearly all (97.7%, 380/389) encourage those at-risk to exercise, including resistance exercise (86.2%, 331/384). Most do not perform axillary reverse mapping (ARM) (67.9%, 264/389) or a lymphatic preventive healing approach (LYMPHA) (84.9%, 331/390). Most (76.1%, 296/389) screen at-risk patients for BCRL. The most frequently used screening tools include self-reported symptoms (81%, 255/315), circumferential tape measure (54%, 170/315) and bioimpedance spectroscopy (27.3%, 86/315). After a BCRL diagnosis, most (90%, 351/390) refer management to a lymphedema-certified physical therapist. For affected patients, nearly all encourage exercise (98.7%, 384/389). Many (49%, 191/390) refer affected patients for consideration of lymphovenous bypass or lymph node transfer. CONCLUSION: Most respondents were unfamiliar with the ASBrS expert panel recommendations for patients at risk for BCRL and those affected by BCRL. Opportunities exist to increase awareness of best practices and to acquire ARM and LYMPHA technical expertise.

Prognosis and Chemotherapy Use in Breast Cancer Patients with Multiple Lymphatic Micrometastases: An NCDB Analysis.

BACKGROUND: The number of involved lymph nodes negatively affects prognosis in breast cancer patients. Nevertheless, current staging and treatment recommendations do not distinguish between patients with single versus multiple lymphatic micrometastases. In this study, we aim to better characterize these patients. METHODS: The National Cancer Database was retrospectively queried to identify 486,800 women with stage I-III, estrogen receptor-positive/progesterone receptor-positive/human epidermal growth factor receptor 2-negative (ER+/PR+/HER2-) breast cancer and nodal status of N0, N1mi with 1 (Nmic1) or more (Nmic > 1) involved nodes, and N1 with 1 involved node (N1.1), from 2010 to 2016. Patients with different nodal statuses were compared regarding treatment characteristics, survival, and benefit from chemotherapy by their 21-gene recurrence score (RS). RESULTS: Of the 23,072 N1mi patients, 88.3% were Nmic1 and 11.7% were Nmic > 1. Nmic > 1 patients were younger, had larger and higher-grade tumors, with more lymphovascular invasion, and were more commonly treated by axillary dissection, radiation, and chemotherapy than Nmic1 patients. In that, they were comparable with N1.1 patients. Five-year survival of Nmic > 1 patients (88.1%) was worse than Nmic1 patients (90.1%; p = 0.02), but similar to N1.1 patients (87.9%). Nmic1, Nmic > 1, and N1.1 patients with RS 11-25 exhibited a < 2% absolute survival benefit associated with chemotherapy. With RS > 25, Nmic > 1 patients showed a 3.5% benefit, similar to Nmic1 (4.8%) and lower than N1.1 (10.9%) patients. CONCLUSIONS: Nmic > 1 breast cancer patients have worse prognoses than Nmic1 patients, similar to N1.1 patients. Our data suggest those patients with RS 11-25 have minimal benefit from chemotherapy. These findings should be taken into account when discussing prognosis and considering chemotherapy in patients with lymphatic micrometastases.

Surgical Jeopardy: Play to Learn.

BACKGROUND: General Surgery residencies use protected education time in various fashions in order to optimize content quality and yield for their learners. This knowledge is tested annually with the American Board for Surgery In-Training Examination (ABSITE) exam and is used to evaluate several aspects of a resident. We hypothesized that using a jeopardy game in educational conference would encourage residents to engage in self-learning and improve ABSITE scores at a single institution. MATERIALS AND METHODS: At a single institution, during protected education conference, residents played an hour-long surgical jeopardy game every 7 wk to summarize high yield topics discussed during the previous 6 wk of didactic learning. A 5-point Likert survey was completed by general surgery residents to discern the utility of the game format for learning. The ABSITE category scores were also evaluated from the year before and the year after the game was implemented. RESULTS: Twenty-four general surgery residents took the survey with >80% agreeing that the jeopardy format was either a fun or an effective way to learn general surgery topics. Additionally, over 80% of residents thought the game format helped with retention of knowledge. ABSITE categories that had a jeopardy session improved from 65.9% to 70.4% correct (P = 0.0003). ABSITE categories that did not have dedicated jeopardy had a non-significant increase in scores (67.7%-69.9%, P = 0.1). CONCLUSIONS: Implementing surgical jeopardy as a component of educational conferences in general surgery resident training is correlated with improvement of ABSITE scores. Surgical jeopardy may be easily adopted and implemented to stimulate self-directed learning for residents.

Doxorubicin Activates Ryanodine Receptors in Rat Lymphatic Muscle Cells to Attenuate Rhythmic Contractions and Lymph Flow.

Doxorubicin is a risk factor for secondary lymphedema in cancer patients exposed to surgery or radiation. The risk is presumed to relate to its cytotoxicity. However, the present study provides initial evidence that doxorubicin directly inhibits lymph flow and this action appears distinct from its cytotoxic activity. We used real-time edge detection to track diameter changes in isolated rat mesenteric lymph vessels. Doxorubicin (0.5-20 µmol/l) progressively constricted lymph vessels and inhibited rhythmic contractions, reducing flow to 24.2% ± 7.7% of baseline. The inhibition of rhythmic contractions by doxorubicin paralleled a tonic rise in cytosolic Ca2+ concentration in lymphatic muscle cells, which was prevented by pharmacological antagonism of ryanodine receptors. Washout of doxorubicin partially restored lymph vessel contractions, implying a pharmacological effect. Subsequently, high-speed optical imaging was used to assess the effect of doxorubicin on rat mesenteric lymph flow in vivo. Superfusion of doxorubicin (0.05-10 µmol/l) maximally reduced volumetric lymph flow to 34% ± 11.6% of baseline. Likewise, doxorubicin (10 mg/kg) administered intravenously to establish clinically achievable plasma concentrations also maximally reduced volumetric lymph flow to 40.3% ± 6.0% of initial values. Our findings reveal that doxorubicin at plasma concentrations achieved during chemotherapy opens ryanodine receptors to induce "calcium leak" from the sarcoplasmic reticulum in lymphatic muscle cells and reduces lymph flow, an event linked to lymph vessel damage and the development of lymphedema. These results infer that pharmacological block of ryanodine receptors in lymphatic smooth muscle cells may mitigate secondary lymphedema in cancer patients subjected to doxorubicin chemotherapy. SIGNIFICANCE STATEMENT: Doxorubicin directly inhibits the rhythmic contractions of collecting lymph vessels and reduces lymph flow as a possible mechanism of secondary lymphedema, which is associated with the administration of anthracycline-based chemotherapy. The inhibitory effects of doxorubicin on rhythmic contractions and flow in isolated lymph vessels were prevented by pharmacological block of ryanodine receptors, thereby identifying the ryanodine receptor family of proteins as potential therapeutic targets for the development of new antilymphedema medications.

Cutting Healthcare Costs with Hematoma-Directed Ultrasound-Guided Breast Lumpectomy.

BACKGROUND: Localization of nonpalpable breast lesions for breast-conserving surgery (BCS) remains highly variable and includes needle/wire localization (NL), radioactive seed localization, radar localization, and hematoma-directed ultrasound-guided (HUG) lumpectomy. The superiority of HUG lumpectomy over NL has been demonstrated repeatedly in terms of safety, accuracy, low positive margin rates, cosmesis, and patient satisfaction. In this study, we evaluate the cost effectiveness of HUG lumpectomy over NL for nonpalpable breast lesions. METHODS: We performed a retrospective review of 569 patients who underwent lumpectomy at the University of Arkansas for Medical Sciences from May 2014 through December 2017. Lumpectomies were stratified by localization technique, i.e. NL versus HUG. A cost-savings estimate was determined for the HUG localization technique, and a total amount of dollars saved over the study period was calculated. RESULTS: Overall, 569 lumpectomies were performed: 501 (88.0%) via HUG and 68 (12.0%) via NL. Intraoperative ultrasound was used in 566 operations (99.5%). Of the lumpectomies performed by HUG, 190 lesions (33.4%) were visible only on mammogram or breast magnetic resonance imaging prior to diagnostic core needle biopsy (CNB). Cost estimates comparing HUG with NL demonstrated a cost savings of $497.00 per procedure, the cost of preoperative needle localization by a radiologist, and a total of $94,430.00 for the study period. CONCLUSION: In utilizing HUG lumpectomy, the initial CNB serves as the diagnostic and localization procedure, thus saving time and a painful second procedure on the day of operation. HUG lumpectomy is safe, accurate, reduces healthcare costs, and results in a better patient experience for the surgical removal of nonpalpable breast lesions.

Steps to Getting Your Manuscript Published in a High-Quality Medical Journal.

Publication of your research represents the culmination of your scientific activities. The key to getting manuscripts accepted is to make them understandable and informative so that your colleagues will read and benefit from them. We describe key criteria for acceptance of manuscripts and outline a multi-step process for writing the manuscript. The likelihood that a manuscript will be accepted by a major journal is significantly increased if the manuscript is written in polished and fluent scientific English. Although scientific quality is the most important consideration, clear and concise writing often makes the difference between acceptance and rejection. As with any skill, efficient writing of high-quality manuscripts comes with experience and repetition. It is very uncommon for a manuscript to be accepted as submitted to a journal. Thoughtful and respectful responses to the journal reviewers' comments are critical. Success in scientific writing, as in surgery, is dependent on effort, repetition, and commitment. The transfer of knowledge through a well-written publication in a high-quality medical journal will have an impact not only in your own institution and country, but also throughout the world.

Does Axillary Reverse Mapping Prevent Lymphedema After Lymphadenectomy?

BACKGROUND: We hypothesized that disconcerting lymphedema rates in both sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) may be because of unrecognized vunerable variations in arm lymphatic drainage within the axilla. Axillary reverse mapping (ARM) facilitates identification and avoidance of arm lymphatics within the axilla and its use may reduce lymphedema. METHODS: This institutional review board-approved study from June 2007 to December 2013 involved patients undergoing SLNB with or without ALND, or ALND alone. Technetium is injected subareolarly for localization of the breast SLN and isosulfan blue dye (5 mL) is injected in the ipsilateral upper arm for localization of nonbreast lymphatics. Data were collected on identification and preservation of arm lymphatics, crossover rates, blue node metastases, axillary recurrence, and lymphedema as measured by volume displacement. RESULTS: A total of 654 patients prospectively underwent 685 ARM procedures with a SLNB and/or ALND. Objective lymphedema rates for SLNB and ALND were 0.8% and 6.5% respectively, with 26-month median follow up. Blue lymphatics were identified in 29.2% (138/472) of SLNB and 71.8% (153/213) of ALND. Crossover was seen in 3.8% (18/472) of SLNB and 5.6% (12/213) of ALND. Blue node metastases rate was 4.5% (2/44). Axillary recurrence rate was 0.2% and 1.4% for SLNB and ALND, respectively. CONCLUSIONS: ARM allows frequent identification of arm lymphatics in the axilla, which would have been transected during routine surgery. Rates of metastases in noncrossover nodes and axillary recurrences are low. Lymphedema rates are dramatically reduced using ARM when compared with accepted standards.

Chemotherapy Significantly Improves Survival for Patients with T1c-T2N0M0 Medullary Breast Cancer: 3739 Cases From the National Cancer Data Base.

BACKGROUND: Medullary breast cancer (MBC) is a rare tumor associated with a better prognosis compared with other breast cancers. The role of adjuvant chemotherapy has not been extensively studied. METHODS: Female patients with invasive MBC reported to the National Cancer Data Base from 2004 to 2012 were analyzed. Overall survival (OS) and treatment were studied using the Kaplan-Meier method and the Cox proportional hazard model. Patients who had node-negative (N0), non-metastatic (M0) tumors 10 to 50 mm in size (T1cN0M0 and T2N0M0) treated with and without chemotherapy were analyzed using propensity score matching. RESULTS: Of 3739 patients with MBC, 2642 (71%) had T1b-T2N0M0 disease treated with and without chemotherapy. Multivariable analysis showed that for all MBC patients, the significant predictors of OS were age older than 65 years, one or more comorbidities, tumor larger than 2 cm, positive nodes, distant metastasis, and treatment with chemotherapy or radiation therapy. Patients with T1cN0M0 and T2N0M0 had improved OS if they received chemotherapy (p < 0.0005). Patients with T1bN0M0 who received chemotherapy did not show better OS than those who did not. Patients with T1c-T2N0M0 were then matched by propensity score based on age, presence of comorbidities, tumor size, and treatment methods used. After matching, the group receiving chemotherapy showed an improved OS (hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.26-0.62; p < 0.0005) compared to the group that did not receive chemotherapy. CONCLUSIONS: For patients with T1c-T2N0M0 MBC, chemotherapy significantly improves OS.

Troubleshooting Sentinel Lymph Node Biopsy in Breast Cancer Surgery.

BACKGROUND: Performing a sentinel lymph node biopsy (SLNB) is the standard of care for axillary nodal staging in patients with invasive breast cancer and clinically negative nodes. The procedure provides valuable staging information with few complications when performed by experienced surgeons. However, variation in proficiency exists for this procedure, and a great amount of experience is required to master the technique, especially when faced with challenging cases. The purpose of this paper was to provide a troubleshooting guide for commonly encountered technical difficulties in SLNB, and offer potential solutions so that surgeons can improve their own technical performance from the collective knowledge of experienced specialists in the field. METHODS: Information was obtained from a convenience sample of six experienced breast cancer specialists, each actively involved in training surgeons and residents/fellows in SLNB. Each surgeon responded to a structured interview in order to provide salient points of the SLNB procedure. RESULTS: Four of the key opinion surgical specialists provided their perspective using technetium-99 m sulfur colloid, and two shared their experience using blue dye only. Distinct categories of commonly encountered problem scenarios were presented and agreed upon by the panel of surgeons. The responses to each of these scenarios were collected and organized into a troubleshooting guide. DISCUSSION: We present a compilation of 'tips' organized as a troubleshooting guide to be used to guide surgeons of varying levels of experience when encountering technical difficulties with SLNB.