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Introduction: The objective of this study was to examine the impact of the early part of the COVID-19 pandemic on the number of newly diagnosed breast cancer cases at Commission on Cancer (CoC)-accredited facilities relative to the United States (U.S.) population., Methods: We examined the incidence of breast cancer cases at CoC sites using the U.S. Census population as the denominator. Breast cancer incidence was stratified by patient age, race and ethnicity, and geographic location., Results: A total of 1,499,806 patients with breast cancer were included. For females, breast cancer cases per 100,000 individuals went from 188 in 2015 to 203 in 2019 and then dropped to 176 in 2020 with a 15.7% decrease from 2019 to 2020. Breast cancer cases per 100,000 males went from 1.7 in 2015 to 1.8 in 2019 and then declined to 1.5 in 2020 with a 21.8% decrease from 2019 to 2020. For both females and males, cases per 100,000 individuals decreased from 2019 to 2020 for almost all age groups. For females, rates dropped from 2019 to 2020 for all races and ethnicities and geographic locations. The largest percent change was seen among Hispanic patients (-18.4%) and patients in the Middle Atlantic division (-18.6%). The stage distribution (0-IV) for female and male patients remained stable from 2018 to 2020., Conclusion: The first year of the COVID-19 pandemic was associated with a decreased number of newly diagnosed breast cancer cases at Commission on Cancer sites., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The objective of this study was to describe patient values and personality traits associated with breast surgery choice for patients with breast cancer., Methods: A survey based on qualitative patient interviews and the Big-Five personality trait profile was distributed to Love Research Army volunteers aged 18-70 years old who underwent breast cancer surgery from 2009 to 2020. Multivariable logistic regression analysis was used to determine independent patient values and personality traits for the choice of breast-conserving surgery (BCS), unilateral mastectomy (UM) and bilateral mastectomy (BM)., Results: 1497 participants completed the survey. Open-mindedness was associated with UM and sociability was associated with BM. A majority of patients prioritized cancer outcomes. Compared to BM patients, BCS and UM patients were significantly more likely to choose values associated with maintaining their self-image, optimizing surgical recovery, and following their doctor's recommendation., Conclusions: Other values besides cancer outcomes differentiate patient surgical choice for BCS or mastectomy., Competing Interests: Declaration of competing interest This work was supported in part by a grant from the John Wayne Cancer Foundation. Otherwise, the authors declare that they have no known competing relationships or financial interests that could have appeared to influence this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The American Society of Breast Surgeons released a consensus statement that genetic testing should be made available to all patients with a personal history of breast cancer. However, it is not clear whether physicians feel comfortable with universal genetic testing (UGT) or if they have sufficient knowledge to interpret results and manage them appropriately., Objective: The purpose of this study was to explore breast surgeons' attitudes toward UGT., Methods: Breast surgeons were consented and scheduled for a semi-structured virtual interview. Transcripts were uploaded into qualitative analysis software where they were exhaustively and iteratively coded. Codes were then organized into higher-order categories and themes and data saturation were assessed., Results: Thirty-one surgeons completed the qualitative interview. Most surgeons practiced in the academic or community setting and most practiced in the Midwest (71.0%). The majority (90.3%) reported having a structured genetics program. The majority (96.8%) referred their patients to genetics for counseling and most preferred ordering testing through a genetic services provider. Some surgeons had concerns about access to genetic services. A minority of surgeons order UGT for all newly diagnosed breast cancer patients. The majority of respondents thought that more training in genetics was needed for surgeons. Many surgeons expressed concern about the psychosocial effects of UGT on patients., Conclusions: Many surgeons expressed concerns about UGT, mainly related to discomfort with their training, access to genetic services, and the psychosocial impact on their patients. Future work is needed to determine how to improve surgeon's comfort level in implementing UGT., (© 2023. Society of Surgical Oncology.)

Introduction: Studies have shown a decrease in bilateral mastectomy (BM) rates over the past five to ten years, but it is not clear if these decreases are the same across different patient races., Methods: Using the National Cancer Database (NCDB) we examined BM rates for patients with AJCC Stage 0-II unilateral breast cancer from 2004 to 2020 for White versus nonwhite races (Blacks, Hispanics, and Asians). Multivariable logistic regression was used to identify patient and facility factors associated with BM by patient race from 2004 to 2006 and 2018-2020., Results: Of 1,187,864 patients, 791,594 (66.6%) had breast conserving surgery (BCS), 258,588 (21.8%) had unilateral mastectomy (UM) and 137,682 (11.6%) had BM. Our patient population was 927,530 (78.1%) White patients, 124,636 (10.5%) Black patients, 68,048 (5.7%) Hispanic patients, and 48,341 (4.1%) Asian patients. The BM rate steadily increased from 5.6% to 15.6% from 2004 to 2013, at which point the BM rate decreased to 11.3% in 2020. The decrease in BM was seen across all races, and in 2020, 6,487 (11.7%) Whites underwent BM compared to 506 (10.7%) Hispanics, 331 (9.2%) Asians, and 723 (9.1%) Blacks. Race was a significant independent factor for BM in 2004-2006 and 2018-2020 but all races were more likely to undergo BM in 2004 compared to 2020 after adjusting for patient and facility factors. Compared to Whites, the odds of undergoing BM were OR 0.41 (0.37-0.45) in 2004 compared to OR 0.66 (0.63-0.69) in 2020 for Blacks, OR 0.44 (0.38-0.52) and OR 0.61 (0.57-0.65) for Asians and OR 0.59 (0.52-0.66) and OR 0.71 (0.67-0.75) for Hispanics, respectively., Conclusion: BM rates for all races have declined since 2013, and differences in rates of BM amongst races have narrowed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Little is known about the experience of the male breast cancer patient. Mastectomy is often offered despite evidence that breast-conserving surgery (BCS) provides similar outcomes., Methods: Two concurrent online surveys were distributed from August to October 2020 via social media to male breast cancer (MBC) patients and by email to American Society of Breast Surgeon members. The MBC patients were asked their opinions about their surgery, and the surgeons were asked to provide surgical recommendations for MBC patients., Results: The survey involved 63 MBC patients with a mean age of 62 years (range, 31-79 years). Five MBC patients (7.9 %) stated that their surgeon recommended BCS, but 54 (85.7 %) of the patients underwent unilateral, and 8 (12.7 %) underwent bilateral mastectomy. Most of the patients (n = 60, 96.8 %) had no reconstruction. One third of the patients (n = 21, 33.3 %) felt somewhat or very uncomfortable with their appearance after surgery. The response rate was 16.5 % for the surgeons. Of the 438 surgeons who answered the survey, 298 (73.3 %) were female, 215 (51.7 %) were fellowship-trained, and 244 (58.9 %) had been practicing for 16 years or longer. More than half of surgeons (n = 259, 59.1 %) routinely offered BCS to eligible men, and 180 (41.3 %) stated they had performed BCS on a man with breast cancer. Whereas 89 (20.8 %) of the surgeons stated that they routinely offer reconstruction to MBC patients, 87 (20.3 %) said they do not offer reconstruction, 96 (22.4 %) said they offer it only if the patient requests it, and 157 (36.6 %) said they never consider it as an option., Conclusions: The study found discordance between MBC patients' satisfaction with their surgery and surgeon recommendations and experience. These data present an opportunity to optimize the MBC patient experience., (© 2022. Society of Surgical Oncology.)

Background: The objective of this study was to examine whether an exercise program and standardized operating room positioning protocol (EOPP) would improve surgeon muscle workload and/or surgeon perception of mental/physical workload for nipple-sparing mastectomy (NSM)., Methods: This prospective study analyzed muscle workload by EMG of four surgeons performing NSM before and after an EOPP. Surveys were administered assessing surgeon perception of mental/physical workload. EMG data were analyzed using repeated-measures ANOVA, controlling for surgeon, first assistant, duration and difficulty of procedure, left or right side, and sequence of the procedure., Results: A total of 56 NSM cases performed by 3 surgeons were analyzed. One surgeon was excluded because of muscle injury and undergoing active physical therapy during the study period. After implementation of the EOPP, the left (P = 0.005) and right (P = 0.020) upper trapezii muscles had a significant decrease in overall ergonomic workload but there was no significant change in overall ergonomic workload for the bilateral cervical erector spinae, anterior deltoid, and lumbar erector spinae muscle groups. When analyzing muscle group exertion by surgeon, there was significant variability in all muscles except the left cervical erector spinae. Following the EOPP, surgeons reported that the procedures were more physically (P = 0.01) and mentally (P = 0.002) demanding and visualization (P = 0.04) was worse. The breast laterality and sequence did not affect muscle exertion., Conclusions: An EOPP decreased the overall ergonomic workload of one muscle group for surgeons performing NSM but did not impact surgeon perception of mental/physical workload. Further investigation is needed to improve surgeon ergonomics., (© 2021. Society of Surgical Oncology.)

Background: The recent data on decision regret of patients undergoing breast cancer surgery are sparse., Methods: An electronic cross-sectional survey was distributed to Love Research Army volunteers ages 18-70 years who underwent breast cancer surgery from 2009 to 2020. Decision regret scores were compared among patients who underwent bilateral mastectomy (BM), unilateral mastectomy (UM), breast-conserving surgery (BCS), and BCS first (BCS followed by re-excision or mastectomy) and between procedures during different time periods. Multivariable logistic regression, adjusted for patient and tumor factors, was used to determine whether surgery type was associated with a regret score in the highest quartile range., Results: The survey was completed by 2148 women, 1525 (71.0%) of whom reported their surgery choice and answered all questions on the regret scale. The mean age of the participants was 50 years, and the median year of surgery was 2014. The median decision regret score for all the patients was 5 (interquartile range [IQR], 0-20) on a 100-point scale. The regret score of 342 participants (22.4%) was 25 or higher (BCS, 20.2%; BCS first, 31.9%; UM, 30.8%; BM, 15.4%; p < 0.001). In the multivariable analysis, BM was associated with less regret than UM (odds ratio [OR], 0.40 (range, 0.27-0.58); p < 0.001), BCS (OR, 0.56 (range, 0.38-0.83; p = 0.003), or BCS first (OR, 0.32; range, 0.21-0.49; p < 0.001). During the three periods analyzed (2009-2012, 2013-2016, and 2017-2020), the BM and BCS patients had the lowest regret scores of all the surgical types., Conclusions: Decision regret was low among the patients undergoing breast cancer surgery but lowest among the BM patients after adjustment for clinical and tumor factors including complications., (© 2021. Society of Surgical Oncology.)

Purpose: To examine how treatment delays brought on by the COVID-19 pandemic impacted the physical and emotional well-being of physicians treating these patients., Methods: A cross-sectional survey of physician breast specialists was posted from April 23rd to June 11th, 2020 on membership list serves and social media platforms of the National Accreditation Program for Breast Centers and the American Society of Breast Surgeons. Physician well-being was measured using 6 COVID-19 burnout emotions and the 4-item PROMIS short form for anxiety and sleep disturbance. We examined associations between treatment delays and physician well-being, adjusting for demographic factors, COVID-19 testing and ten COVID-19 pandemic concerns., Results: 870 physicians completed the survey, 61% were surgeons. The mean age of physicians was 52 and 548 (63.9%) were female. 669 (79.4%) reported some delay in patient care as a result of the COVID-19 pandemic. 384 (44.1%) and 529 (60.8%) of physicians scored outside normal limits for anxiety and sleep disturbance, respectively. After adjusting for demographic factors and COVID-19 testing, mean anxiety and COVID-19 burnout scores were significantly higher among physicians whose patients experienced either delays in surgery, adjuvant chemotherapy, radiation, breast imaging or specialty consultation. A multivariable model adjusting for ten physician COVID-19 concerns and delays showed that "delays will impact my emotional well-being" was the strongest concern associated with anxiety, sleep disturbance and COVID-19 burnout factors., Conclusions: Breast cancer treatment delays during the initial surge of the COVID-19 pandemic in the United States were associated with a negative impact on physician emotional wellness.

Purpose: More women with unilateral early stage breast cancer are electing bilateral mastectomy (BM). Many cite anxiety, fear of recurrence, and certain aesthetic desires in their decision-making. Yet conflicting data exist regarding how these factors both inform and are modulated by medical decision-making, especially among women eligible for breast conservation (BCT). This study sought to assess the trajectories of women undergoing various surgical procedures for breast cancer., Methods: We performed a prospective longitudinal study of women with unilateral, non-hereditary breast cancer who underwent BCT, unilateral mastectomy (UM), or BM. Women completed surveys before surgery and at 1, 9, and 15 months postop. Surveys included questions about treatment preferences, decisional control, the HADS-A anxiety scale, the Fear of Relapse/Recurrence Scale (FRRS), and the BREAST-Q. The Kruskal-Wallis test was used to compare outcomes between BCT, UM, and BM groups at each time point., Results: 203 women were recruited and 177 (87.2%) completed 15-month follow-up. Of these, 101 (57.0%) underwent BCT, 33 (18.6%) underwent UM, and 43 (24.2%) underwent BM. Generalized anxiety and FRRS scores were similar between BCT, UM, and BM groups and declined uniformly after surgery. Although baseline breast satisfaction was similar between groups, at 15 months, it was significantly lower in BM patients than in BCT patients. Women who felt "very" confident and "very" informed before surgery had lower anxiety, lower fear of recurrence, better psychosocial well-being (PSWB), and greater breast satisfaction at 15 months., Conclusion: While patients who undergo mastectomy have less long-term breast satisfaction, all patients can expect to experience similar improvements in anxiety and PSWB. Efforts should be made to ensure that patients are informed and confident regardless of which surgery is chosen, for this is the greatest predictor of better outcomes.

A modern perspective on the nipple-sparing mastectomy (NSM) looking at current indications as well as the most up-to-date evidence both in the literature and from our institution. There is an in-depth description of our NSM technique and an overview of alternative approaches, including the robotic technique. The complicated concept of the learning curve is addressed and ideas on how to train other NSM adopters., (© 2020 Wiley Periodicals, Inc.)

Background: Few decision aids for newly diagnosed breast cancer patients are used by surgeons during their consultations with patients., Methods: From 2017 to 2019, an online interactive breast cancer in-visit decision aid (BIDA) was used on 63 patients and 57 patients underwent usual care (UC). We compared knowledge, decision involvement, anxiety and distress (HADS scale), quality of life (PROMIS), fear of recurrence, body image, and patient values between BIDA and UC before surgery. A knowledge score of ≥ 57% was considered "high knowledge.", Results: A total of 188 patients were enrolled of which 120 (63.8%) completed all study procedures. Patient demographic characteristics and anxiety and quality of life (QOL) at baseline were similar between patients in BIDA and UC cohorts. After seeing the surgeon, patients in the BIDA group had higher composite knowledge scores compared with UC patients [n = 55 (87.3%) vs. n = 39 (68.4%) respectively, p = 0.012]. Patients in the BIDA cohort reported being asked more often their surgical preference (p = 0.013) and discussing bilateral mastectomy (BM) as an option (p = 0.048). There was a trend of less patients in the BIDA cohort undergoing BM then in the UC cohort [10 (15.9%) vs. 14 (24.6%), p = 0.49]. Anxiety and distress, QOL, fear of recurrence, and body image were not significantly different between BIDA and UC cohorts., Conclusions: A decision aid used by surgeons during their consultation was associated with higher knowledge levels, patients reporting more discussion about BM, and a trend of lower BMs. A larger study with more patients is needed to confirm this finding.

Background: Nipple-sparing mastectomies (NSMs) with reconstruction are believed to be more difficult to perform than skin-sparing mastectomies (SSMs), but there is little quantitative data to support this claim., Methods: This prospective study analyzed four surgeons performing mastectomies. Electromyography (EMG) electrodes placed on selected muscle groups on each surgeon were used to capture muscle exertion intraoperatively and a percentage of maximum voluntary exertion was calculated (%MVE). Data regarding surgeon demographics, exercise habits, musculoskeletal problems, and surgery-specific workload was collected using a questionnaire., Results: A total of 61 mastectomies were analyzed; 40 were NSM and 21 were SSM/total mastectomies. NSM were considered to be more mentally demanding and physically demanding than SSM (p < 0.001). When the surgeons' EMG data was analyzed as a group, there was a statistically significant difference in %MVE for NSM versus SSM at high muscle activity in bilateral anterior deltoid muscle groups and at average muscle activity for the left anterior deltoid muscle only. At low muscle activity, there was a statistically significant increase in activation for SSM versus NSM in bilateral cervical erector spinae. Repeated measures ANOVA was performed, which showed statistically significant differences at high muscle activity between NSM and SSM in the left cervical erector spinae and bilateral anterior deltoid muscles., Conclusions: Our pilot study shows that intraoperative EMGs can assess muscle activity for mastectomy operations and show a difference between NSM and SSM. This is the first study to provide quantitative data on muscle strain with NSM.

Background: The utilization of OncotypeDx in the setting of neoadjuvant chemotherapy (NCT) is not well defined. The objective of this study was to determine what proportion of hormone receptor (HR)-positive patients undergoing NCT would not benefit from chemotherapy based on OncotypeDx recurrence scores (RS) and predictors of a high RS as defined by the TAILORx trial., Methods: The National Cancer Data Base was used to identify patients with unilateral clinical stage I-III HR+/Her2- breast cancer who had an OncotypeDx score and who had undergone NCT. Patients undergoing adjuvant chemotherapy were used as a comparison group., Results: Of 307,666 patients, 41.8% had testing with OncotypeDx. Of these, 76.6% had no chemotherapy, 22.3% adjuvant chemotherapy, and 1.1% NCT. OncotypeDx testing in NCT patients increased from 4.9% in 2010 to 8.2% in 2015. Of NCT patients with OncotypeDx testing, 11.6% had RS < 11, 44.4% RS 11-25, and 43.9% RS > 25. In patients age ≤ 50 years, 14.5% had RS < 11, 12.4% RS 11-15, 31.4% RS 16-25, and 41.7% RS > 25. Predictors of RS > 25 on multivariable analysis included grade 3 tumors (odds ratio [OR] 3.83) and PR-negative tumors (OR 5.26) but not clinical T or N stage (p > 0.05)., Conclusions: More than half of patients with OncotypeDx testing are being overtreated with NCT, and a third of younger patients are being overtreated. Predictors of a high RS are reliably available at core biopsy, suggesting an application of OncotypeDx in determining the need for NCT for some HR-positive breast cancers.

Background: In 2014, the Society of Surgical Oncology and American Society for Radiation Oncology guidelines defined negative margin for stage I and II breast cancer as "no tumor on ink." We hypothesized that repeat operation rates have decreased since the guideline introduction and would be associated with changes in overall surgical trends., Study Design: The National Cancer Database was used to identify women who underwent initial breast-conserving surgery (BCS) for stage I and II breast cancer from 2004 to 2015., Results: Of 521,578 patients that underwent initial BCS, 82.7% had BCS alone and 17.3% had repeat operation: 67% with BCS followed by another BCS, 24% with BCS followed by unilateral mastectomy, and 9% with BCS followed by bilateral mastectomy (BM). The repeat operation rate decreased from 16.2% in 2004 to 14.0% in 2015 (p < 0.01). Breast-conserving surgery with repeat BCS decreased from 12.8% to 9.7%, and BCS followed by BM increased from 0.7% in 2004 to 1.9% 2013, then decreased to 1.4% in 2015. Trends for all surgical patients regardless of initial procedure showed a BCS rate of 64.0% in 2013 that increased to 67.6% in 2015. The BM rate increased from 4.6% in 2004 to 13.6% in 2013, then decreased to 12.8% in 2015 (p < 0.05). Adjusted multivariable regression found independent predictors of repeat operation to be diagnosis before 2014 (odds ratio [OR] 1.25), age younger than 50 years (OR 1.70), Her2neu receptor-positive tumors (OR 1.61), and lobular histology (OR 1.61)., Conclusions: Repeat operation rates are decreasing after 2014, which is also associated with a rise in BCS and decrease in BM rates. Dissemination of margin guidelines for early-stage breast cancer might be impacting overall surgical trends., (Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: We examined axillary surgery in mastectomy patients with tumor-positive nodes and how the type of axillary surgery impacted use of postmastectomy chest wall radiation therapy (PMRT)., Methods: Using the National Cancer Data Base, we selected patients with AJCC cT1/T2c N0 breast cancer with one to three tumor-positive lymph nodes treated between 2013 and 2014. Type of axillary surgery was analyzed using the FORDS scope of regional lymph node surgery variable. Multivariable logistic regression modeling was used to identify independent predictors associated with SNB alone and the use of PMRT., Results: Of 8089 patients, 2482 (30.7%) underwent SNB alone, 1339 (16.6%) underwent axillary dissection (ALND) alone, and 4268 (52.7%) underwent SNB followed by ALND. Fifty-seven percent of patients with micrometastases underwent SNB alone compared with 22.6% of patients with macrometastases. Independent predictors of SNB alone for patients with micrometastases were African American race, number of nodes positive, and PMRT. For patients with macrometastases, age, facility type and location, and PMRT were independent predictors for SNB alone. Of 2449 patients who underwent SNB alone, 1538 (62.8%) had no PMRT, 261 (10.7%) had PMRT alone, and 650 (26.5%) had PMRT with regional nodal irradiation. Patients undergoing SNB alone were 1.70 times [96% confidence interval (CI) 1.45-2.00] more likely to undergo PMRT than upfront ALND and 1.51 times (96% CI 1.34-1.71) more likely than SNB followed by ALND., Conclusions: Surgeons are omitting completion ALND in a third of early-stage, node-positive mastectomy patients. SNB alone patients are more likely to undergo PMRT than patients undergoing ALND.

Background: Accelerated partial breast irradiation (APBI) was developed to address disadvantages of overall treatment time and potentially unnecessary radiation associated with whole breast irradiation (WBI). We report updated results of our single institution study using an external beam APBI regimen with a median follow-up of 8 years., Methods: A total of 290 APBI patients with AJCC Stage 0-II breast cancer were compared with 290 WBI patients with matched tumor characteristics. Toxicities were scored based on the Common Terminology Criteria for Adverse Events (CTCAE v3.0). Cox regression models were used to predict likelihood of freedom from ipsilateral failure., Results: Median follow-up was 8 years in the APBI group and 7.5 years in the WBI group. In the APBI group, there were 18 (6.2%) ipsilateral breast tumor recurrence (IBTR), 13 (72%) had elsewhere failures (EF), and 5 (28%) had local failures (LF) with a median time to failure of 64.1 months. In the WBI group, there were three (1.0%) IBTR; one (33%) was an EF and two (67%) were LF with a median time to failure of 91 months. APBI was 4.6 times more likely (hazard ratio 4.57, 95% confidence interval 1.3-16.2, p = 0.02) to have an IBTR than WBI after adjusting for age, tumor size, histology, grade, and estrogen receptor status. Fatigue, erythema, and desquamation toxicities were significantly less in the APBI group then the WBI group., Conclusions: IBTR rates were higher in external beam APBI group compared with WBI, but APBI had fewer toxicities. Clinicians must weigh the risks and benefits of APBI when making a recommendation for partial breast irradiation after lumpectomy.

In 2010, the ACOSOG Z0011 trial showed equivalent survival and recurrence between sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND) for those with a tumor positive sentinel node (SN). We examined national trends in axillary surgery following neoadjuvant chemotherapy (NAC) for clinically node positive disease in the years prior to and after the Z0011 trial publication. 12,063 women with cT1-4N1M0 invasive breast cancer who underwent NAC from 2006 to 2013 and had 1-3 positive nodes on pathology were selected from the National Cancer Data Base. We defined SLNB as 1-4 nodes and ALND as ≥10 nodes examined. 2,704 women (22.4%) underwent SLNB alone and 9,359 (77.6%) underwent ALND. The rate of SLNB increased from 25.6% in 2006 to 33.3% in 2012 in patients that underwent lumpectomy (p < 0.01) and increased from 20.6% to 22.8% in patients that underwent mastectomy (p = 0.25). Patients treated at Community centers (30.4% versus 19.2% at Academic centers) and those with less positive nodes (32.2% for 1 positive node versus 10.1% for 3 positive nodes, p < 0.01) were more likely to have SLNB alone compared to ALND. On multivariate analysis, treatment with lumpectomy (OR 1.46, CI 1.28-1.67), lower number of positive nodes (OR 3.98, CI 3.29-4.82) and lobular subtype (OR 1.82, CI 1.42-2.34) were independent predictors of receiving SLNB alone after NAC. Approximately 22% of patients with cN1 breast cancer underwent SLNB alone for pN1 disease after NAC. Ongoing clinical trials will determine if recurrence and survival rates are equivalent between SLNB and ALND groups., (© 2017 Wiley Periodicals, Inc.)

Background: The role of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy (NAC) and mastectomy is unclear, especially in patients that have post-treatment tumor negative axillary nodes (ypN0)., Methods: The National Cancer Data Base was used to identify women that had PMRT after NAC and mastectomy for clinically node positive (cN1-2) disease from 2004 to 2008. Median follow-up time was 69 months., Results: 8,321 patients were included for analysis, and 6140 (65.6%) had cN1 disease and 2181 (23.3%) had cN2 disease. On adjusted survival analysis, PMRT was associated with an overall survival (OS) benefit in both patients with cN1 (5-yr OS 75.8% vs. 71.9%, P < 0.01) and cN2 (5-yr OS 69.2% vs. 58.6%, P < 0.01) disease. In the subgroup of patients that were ypN0 after NAC, there was no significant survival difference (P > 0.11) for PMRT compared to those patients who were not ypN0, except for patients with hormone-receptor negative tumors, who had improved OS with PMRT (HR 0.65, P < 0.01)., Conclusions: PMRT is associated with improved OS in patients with cN1 and cN2 disease after NAC and mastectomy. However, in the subgroup of patients that were ypN0 after NAC, PMRT improved OS for hormone-receptor negative patients but not hormone-receptor positive patients., (© 2017 Wiley Periodicals, Inc.)

Background: Studies have reported that breast cancer patients have limited understanding about the oncologic outcomes following contralateral prophylactic mastectomy (CPM). We hypothesized that an in-visit decision aid (DA) would be associated with higher patient knowledge about the anticipated short and long term outcomes of CPM., Methods: We piloted a DA which used the SCOPED: (Situation, Choices, Objectives, People, Evaluation and Decision) framework. Knowledge, dichotomized as "low" (≤3 correct) versus "high" (≥4 correct), was assessed immediately after the visit by a 5 item survey. There were 97 DA patients (response rate 62.2 %) and 114 usual care (UC) patients (response rate 71.3 %)., Results: Patient demographic factors were similar between the two groups. Twenty-one (21.7 %) patients in the DA group underwent CPM compared with 18 (15.8 %) in the UC group (p = 0.22). Mean and median knowledge levels were significantly higher in the DA group compared with the UC group for patients of all ages, tumor stage, race, family history, anxiety levels, worry about CBC, and surgery type. Eighty-six (78.9 %) of UC versus 35 (37.9 %) DA patients had low knowledge. Of patients who underwent CPM, 15 (83.3 %) in the UC cohort versus 5 (25.0 %) of DA patients had "low" knowledge., Conclusions: Knowledge was higher in the DA group. The UC group had approximately three times the number of patients of the DA group who were at risk for making a poorly informed decision to have CPM. Future studies should assess the impact of increased knowledge on overall CPM rates.

Purpose Gene expression profiling assays are frequently used to guide adjuvant chemotherapy decisions in hormone receptor-positive, lymph node-negative breast cancer. We hypothesized that the clinical value of these new tools would be more fully realized when appropriately integrated with high-quality clinicopathologic data. Hence, we developed a model that uses routine pathologic parameters to estimate Oncotype DX recurrence score (ODX RS) and independently tested its ability to predict ODX RS in clinical samples. Patients and Methods We retrospectively reviewed ordered ODX RS and pathology reports from five institutions (n = 1,113) between 2006 and 2013. We used locally performed histopathologic markers (estrogen receptor, progesterone receptor, Ki-67, human epidermal growth factor receptor 2, and Elston grade) to develop models that predict RS-based risk categories. Ordering patterns at one site were evaluated under an integrated decision-making model incorporating clinical treatment guidelines, immunohistochemistry markers, and ODX. Final locked models were independently tested (n = 472). Results Distribution of RS was similar across sites and to reported clinical practice experience and stable over time. Histopathologic markers alone determined risk category with > 95% confidence in > 55% (616 of 1,113) of cases. Application of the integrated decision model to one site indicated that the frequency of testing would not have changed overall, although ordering patterns would have changed substantially with less testing of estimated clinical risk-high or clinical risk-low cases and more testing of clinical risk-intermediate cases. In the validation set, the model correctly predicted risk category in 52.5% (248 of 472). Conclusion The proposed model accurately predicts high- and low-risk RS categories (> 25 or ≤ 25) in a majority of cases. Integrating histopathologic and molecular information into the decision-making process allows refocusing the use of new molecular tools to cases with uncertain risk.

Background: There has been a trend toward minimizing surgery in elderly women with estrogen receptor-positive (ER+) breast cancer., Methods: Using the National Cancer Data Base, we selected 95,357 women ≥80 years with invasive, ER+ breast cancer. Chi-square test and logistic regression were used to analyze trends in surgery and hormone therapy., Results: From 2004 to 2012, 90% of women were treated with surgery first and 10% were treated with primary nonoperative management. Of those undergoing nonoperative management, 72% received endocrine therapy and 27% had no treatment. The rate of primary nonoperative treatment doubled from 7% in 2004 to 14% in 2012. Multivariate logistic regression adjusted for patient, facility, and tumor factors identified more advanced clinical stage, older age, African-American race, and treatment at Academic facilities as independent predictors of receiving primary nonsurgical management., Conclusions: There has been an increase over time in primary nonoperative management of ER+ breast cancer in octogenarians., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Studies have shown that contralateral breast cancer (CBC) portends worse survival compared to unilateral breast cancer (UBC), but few studies have been conducted in the United States, and survival is usually examined from the time of CBC development., Methods: Utilizing the Surveillance, Epidemiology, and End Results database, we selected 83,001 newly diagnosed breast cancer patients from 1998 to 2005. The time interval between the initial cancer and CBC was used as a time-dependent variable in a Cox regression analysis to examine overall survival (OS) and disease-specific survival (DSS) between UBC and CBC., Results: Overall, 2130 patients (2.6 %) developed a CBC, 47.2 % within 5 years and 52.8 % ≥ 5 years. Most stage I patients (61.9 %) developed a stage I CBC, and a majority of stage II patients (51.6 %) developed a stage I CBC (p < 0.001). There was a median follow-up of 8.7 years. After adjustment, patients who developed a CBC 4 years after their initial breast cancer had worse DSS compared to patients with UBC (hazard ratio 1.36, 95 % confidence interval 1.03-1.79). Those patients who developed their CBC 8 years after their initial breast cancer had improved DSS (hazard ratio 0.37, 95 % confidence interval 0.20-0.67). Similar trends were observed for OS. Similar trends for OS and DSS were observed for estrogen receptor-negative women and women <50 years old., Conclusions: Development of a CBC early is associated with worse survival, but CBC development later on is associated with improved survival. Future studies are needed that can assist physicians with how to predict whether a patient will develop a CBC early on.

Background: The Z0011 trial showed similar outcomes between sentinel node biopsy (SNB) alone and axillary node dissection (ALND) for early-stage breast cancer, but few studies have examined Z0011's impact on practice patterns., Study Design: Using the National Cancer Data Base, we examined use of SNB alone in patients who did and did not fulfill Z0011 eligibility criteria from 1998 to 2011. Because the National Cancer Data Base does not specifically identify SNB vs ALND, we categorized removal of ≤4 nodes as SNB only and ≥10 nodes as ALND., Results: Of 74,309 lumpectomy patients who fulfilled Z0011 criteria; 17,630 (23.7%) had a ≤4 nodes removed, 15,619 (21.0%) had 5 to 9 nodes removed, and 41,060 (55.3%) had ≥10 nodes removed. The proportion of lumpectomy patients receiving SNB increased from 6.1% in 1998 to 23.0% in 2009 to 56.0% in 2011 (p < 0.001). Independent predictors of ALND in lumpectomy patients were triple-negative tumors, younger than 50 years old, African-American race, size ≥3.0 cm, ≥2 positive nodes, invasive lobular carcinoma, grade III disease, and lymph node macrometastases. Patients outside of Z0011 criteria also underwent SNB alone: 54% of patients with tumors >5 cm, 52.5% who received no radiation therapy or accelerated partial breast irradiation, 35.9% with clinically positive nodes, 22.3% who underwent mastectomy, and 12.9% who had >3 tumor-positive nodes., Conclusions: The use of SNB alone for patients fulfilling Z0011 criteria has increased substantially from 2009 to 2011. A considerable proportion of patients falling outside of Z0011 eligibility criteria were also treated with SNB alone., (Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The rate of contralateral prophylactic mastectomy (CPM) for unilateral breast cancer has increased over the past decade, particularly for young women. This study investigates the impact of race and socioeconomic status (SES) on use of CPM., Study Design: Using the National Cancer Data Base (NCDB), we selected 1,781,409 stage 0 to II unilateral breast cancer patients between 1998 and 2011. Trends in use of CPM by race and SES were analyzed using chi-square tests and logistic regression models., Results: For women of all ages, rates of CPM increased, from 1.9% in 1998 to 10.2% in 2011 (p < 0.001), with higher rates in women ≤45 years old, rising from 3.7% in 1998 to 26.2% in 2011 (p < 0.001). Among young women, white women had the greatest increase in CPM from 4.3% in 1998 to 30.2% in 2011 (p < 0.001). In 2011, CPM rates were 30.2% for white, 18.5% for Hispanic, 16.5% for black, and 15.2% for Asian patients (p < 0.001). The gap in CPM use between white and minority patients persisted in every SES classification, geographic region, and facility type. On multivariate analysis, minority women were 50% less likely to undergo CPM than white women were., Conclusions: Young, white, breast cancer patients are twice as likely to undergo CPM compared with women in other racial groups, even after accounting for pathologic, patient, and facility factors. Variations in shared decision-making processes between women of different backgrounds may contribute to these trends, supporting the need for future studies investigating decision-making processes and decisional aids., (Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Few large-scale multicenter studies have examined wait times for breast surgery and no benchmarks exist., Methods: Using the National Cancer Data Base, we analyzed time from diagnosis to first surgery for 819,175 non-neoadjuvant AJCC stage 0-III breast cancer patients treated from 2003 to 2011. Chi-square tests and logistic regression models were used to examine factors associated with delays to surgery and adjuvant chemotherapy., Results: Seventy percent of patients underwent an initial lumpectomy (LP), 22% a mastectomy (MA), and 8% a mastectomy with reconstruction (MR). The median time from diagnosis to first surgery significantly increased by approximately 1 week for all three procedures over the study period. In a multivariate analysis, the following variables were independent predictors of a longer wait time to first surgery: increasing age, black or Hispanic race, Medicaid or no insurance, low-education communities and metropolitan areas, increasing comorbidities, stage 0 and grade 1 disease, academic/research facilities, high-volume facilities, and facilities located in the New England, Mid-Atlantic, and Pacific regions. In 2010-2011, patients who waited >30 days for surgery were 1.36 times more likely (OR = 1.36, 95% CI 1.30-1.43) to experience a delay to adjuvant chemotherapy >60 days compared with patients who were surgically treated within 30 days of diagnosis., Conclusions: Facility and socioeconomic factors are most strongly associated with longer wait times for breast operations, and delays to surgery are associated with delays to adjuvant chemotherapy initiation.

Background: Several studies have shown that contralateral prophylactic mastectomy (CPM) provides a disease-free and overall survival (OS) benefit in young women with estrogen receptor (ER)-negative breast cancer. We utilized the National Cancer Data Base to evaluate CPM's survival benefit for young women with early -stage breast cancer in the years that ER status was available., Methods: We selected 14,627 women ≤45 years of age with American Joint Committee on Cancer stage I-II breast cancer who underwent unilateral mastectomy or CPM from 2004 to 2006. Five-year OS was compared between those who had unilateral mastectomy and CPM using the Kaplan-Meier method and Cox regression analysis., Results: A total of 10,289 (70.3 %) women underwent unilateral mastectomy and 4,338 (29.7 %) women underwent CPM. Median follow up was 6.1 years. After adjusting for patient age, race, insurance status, co-morbidities, year of diagnosis, ER status, tumor size, nodal status, grade, histology, facility type, facility location, use of adjuvant radiation and chemohormonal therapy, there was no difference in OS in women <45 years of age who underwent CPM compared towith those who underwent unilateral mastectomy (hazard ratio [HR] = 0.93; p = 0.39). In addition, Tthere was no improvement in OS in women <45 years of age with T1N0 tumors who underwent CPM versus unilateral mastectomy (HR = 0.85; p = 0.37) after adjusting for the aforementioned factors. Among women ≤45 years of age with ER-negative tumors who underwent CPM, there was no improvement in OS compared with women who underwent unilateral mastectomy (HR = 1.12; p = 0.32) after adjusting for the same aforementioned factors., Conclusions: CPM provides no survival benefit to young patients with early-stage breast cancer, and no benefit to ER-negative patients. Future studies with longer follow-up are required in this cohort of patients.

Background: Data on recent trends and correlates of utilization for accelerated partial breast irradiation using brachytherapy (APBI-b) for ductal carcinoma in situ (DCIS) are lacking., Methods: This study included 113,841 DCIS patients from the National Cancer Data Base, of whom 8,709 (6.5 %) underwent APBI-b and 105,132 (93.5 %) underwent external beam irradiation after lumpectomy between 2003 and 2011. Trends in APBI-b use, American Society for Radiation Oncology (ASTRO) guideline concordance, and independent factors related to APBI-b use were examined., Results: APBI-b use increased from 1.6 % in 2003 to 11.9 % in 2008 and then decreased to 9.1 % in 2011 (p < 0.001). Before 2009, 24.6 % of patients undergoing APBI-b were in the ASTRO guideline 'unsuitable' category, but this proportion decreased to 14.6 % after 2009 (p < 0.001). When adjusting for year of diagnosis, patient, tumor, and facility factors, the four strongest independent factors for APBI-b use were year of diagnosis followed by facility location, facility volume, and facility type. APBI-b use was highest in the East South Central census region (13.1 %) and lowest in the New England region (2.0 %). A statistically significant interaction was identified between facility type and volume. Patients in community cancer programs of large volume were more likely to receive APBI-b, whereas patients in larger academic programs were less likely to receive APBI-b., Conclusion: APBI-b for DCIS decreased from 2008 to 2011. After year of diagnosis, facility factors were most strongly associated with APBI-b use as opposed to patient and tumor factors. Reasons for these trends are multifactorial and deserve further study.

Background: Rates of bilateral mastectomy (BM) have increased, but the impact on length of stay (LOS), readmission rate, 30-day mortality, and time to adjuvant therapy is unknown., Methods: Using the National Cancer Data Base, we selected 390,712 non-neoadjuvant AJCC stage 0-III breast cancer patients who underwent either unilateral mastectomy (UM) or BM from 2003 to 2010 with and without reconstruction. We used chi-square and logistic regression models for the analysis., Results: A total of 315,278 patients (81 %) had UM, and 75,437 (19 %) had BM; 97,031 (25 %) underwent reconstruction. The number of median days from diagnosis to UM increased from 19 days in 2003 to 28 days in 2010, and for BM, increased from 21 to 31 days (p < 0.001). BM was independently associated with a longer time to surgery when adjusting for patient, facility, and tumor factors and reconstruction (OR 1.11; 95 % CI 1.07-1.15; p < 0.001). Reconstructed patients were twice as likely to have a longer time to surgery (OR 2.07; 95 % CI 2.01-2.14; p < 0.001). The median LOS was 1 day (range 0-184 days) for UM versus 2 (range 0-182) for BM (p < 0.001); 30-day mortality and readmission rates were not different between BM and UM. The median number of days from diagnosis to definitive chemotherapy, hormonal therapy, and radiation therapy was significantly greater in the BM group., Conclusions: Delays to surgical and adjuvant treatment are significantly longer for BM irrespective of reconstruction, and these delays have increased over the study period. These findings can be used by clinicians to counsel patients on BM.

Background: The purpose of this study was to determine if newly diagnosed breast cancer patients undergoing contralateral prophylactic mastectomy (CPM) experience more complications than patients undergoing unilateral mastectomy (UM)., Methods: A total of 600 patients underwent either UM or CPM between January 2009 and March 2012 for unilateral breast cancer. Operative complications were classified as minor (aspirations, infection requiring antibiotics, partial flap and nipple necrosis, minor bleeding, delayed wound healing) or major (hematoma or seroma requiring operation, infection requiring rehospitalization, blood product transfusion, total flap or nipple loss, implant removal), mixed (both minor and major complications), or multiple. Chi-square and multivariate logistic regressions were used for the analysis., Results: Of the 600 patients, 391 (65 %) underwent UM and 209 (35 %) underwent CPM. Across all complication groups, there were significantly more complications in the CPM group versus the UM group (41.6 vs. 28.6 %, p = 0.001). Major complications alone were significantly greater in the CPM versus the UM group (13.9 vs. 4.1 %, p < 0.001). When adjusting for age, body mass index, smoking and diabetes history, AJCC stage, reconstruction, previous radiation therapy, and adjuvant therapy, CPM patients were 1.5 times more likely to have any complication (odds ratio [OR] 1.53; 95 % CI 1.04-2.25, p = 0.029) and 2.7 times more likely to have a major complication compared with UM patients (OR 2.66; 95 % CI 1.37-5.19, p = 0.004)., Conclusions: CPM patients have an increased risk of complications, especially major complications requiring rehospitalization or reoperation. These complications may influence patient and physician decisions to choose CPM.

Background: Randomized trials have not demonstrated a survival benefit for axillary dissection in the elderly, but the use of axillary staging for women 70 years of age and older remains controversial., Methods: We utilized the National Cancer Data Base to study the use of axillary staging from 2004 to 2010 on 102,026 clinically node-negative and estrogen receptor-positive cases of pT1N0 tumors. Chi-square and logistic regression models were used to determine the trends and factors related to axillary staging., Results: Axillary nodes were examined in 88.9 % of the total cohort, and the trend significantly increased from 87.7 % in 2004 to 89.2 % in 2010. A total of 77.2 % of patients underwent lumpectomy and 22.8 % mastectomy, with 87.0 % of lumpectomy patients undergoing axillary staging compared to 95.5 % of mastectomy patients. Predictors of axillary staging examined were age, comorbidity, income, histology, grade, facility type, facility location, and population density. The strongest independent predictor of axillary staging was age: 96.0 % of women aged 70-75 years underwent axillary staging, versus 92.3 % of women 75-80 years old, 83.2 % of women 80-85 years old, 66.5 % of women 86-90 years old, and 45.6 % of women >90 years old. Patients treated at academic/research facilities were 18.5 % less likely (odds ratio 0.81, 95 % confidence interval 0.76-0.87) than community cancer programs to undergo axillary staging. There was significant regional variation among U.S. Census regions: patients treated in the Midwest were 3.8 times more likely to undergo axillary staging than those treated in the Northeast., Conclusions: Despite data indicating decreased utility, axillary staging remains overutilized in women with advancing age.

Background: Previous studies have demonstrated an increase in the utilization of accelerated partial-breast irradiation via brachytherapy (APBI-b), but larger, more contemporary studies examining overall APBI use are lacking., Methods: A total of 575,438 nonneoadjuvant American Joint Committee on Cancer stage 0 to II breast conservation patients were selected from the National Cancer Data Base from 2003 to 2010 who underwent either whole-breast irradiation or APBI., Results: Overall, 59,396 patients (10.3 %) underwent APBI. The use of APBI for the entire cohort increased from 3.4 % in 2003 to 12.8 % (p < 0.001) in 2008 and then decreased to 12.4 % in 2010. Three-dimensional conformal radiation increased from 0.8 to 2.2 %, intensity-modulated radiotherapy increased from 0.7 to 1.3 %, and brachytherapy (APBI-b) increased from 2.0 to 8.9 %. The most significant factors associated with APBI use were patient age and facility location. Patients 80-89 years old were 3.8 times more likely to undergo APBI compared to patients 30-39 years old (odds ratio [OR] 3.77, 95 % confidence interval [CI] 3.45-4.10, p < 0.001). Patients living in the West census region were 2.0 times more likely to undergo APBI compared to patients living in the Northeast (OR 2.0, 95 % CI 1.93-2.15, p < 0.001). Using the American Society of Radiation Oncology (ASTRO) guidelines, among patients with noninvasive cancer who received APBI, 95.6 % were categorized as "cautionary" and 4.4 % as "unsuitable." Of the invasive patients, 43.8 % were categorized as "suitable," 47.0 % as "cautionary," and 9.2 % as "unsuitable.", Conclusions: The utilization of APBI has stabilized at approximately 12 % starting in 2008. The majority of APBI is delivered using APBI-b, with patient age being the most significant factor associated with APBI use.

Determining whether cancer has spread to locoregional lymph nodes is a critical step in the initial staging of breast cancer patients. Although axillary dissection reliably identifies nodal metastases and prevents the recurrence of cancer in the axilla, there is a significant incidence of long-term side effects, notably lymphedema, and the procedure is of no therapeutic benefit in women without axillary metastases. With the advent of sentinel lymph node biopsy, the axilla can be accurately staged in patients with T1-T3, clinically node-negative breast cancers while avoiding the morbidity of axillary lymph node dissection if the nodes do not contain cancer. Recent clinical trials suggest that for women with metastases to 1 or 2 sentinel nodes, the radiation and systemic therapy that are part of modern multimodality breast cancer treatment can replace axillary dissection when breast-conserving therapy is undertaken. For those with greater disease burden or those undergoing mastectomy, axillary dissection remains standard management.

Purpose: Regional failure rates are low in patients with a positive sentinel lymph node biopsy (SLNB) who undergo breast-conserving therapy without axillary lymph node dissection (ALND). The applicability of these findings to total mastectomy (TM) patients is not established. Our aims were to evaluate the characteristics and outcomes of SLNB-positive TM patients who did not receive axillary-specific treatment and to compare them to similar patients who underwent breast-conserving surgery (BCS)., Methods: A total of 535 patients with early-stage breast cancer who underwent definitive breast surgery (210 TM, 325 BCS), had a positive SLNB and did not receive ALND between 1997 and 2009 were identified from an institutional database. Characteristics and outcomes were compared between the TM and BCS groups., Results: Most patients had stage I to IIA, estrogen receptor-positive, progesterone receptor-positive, Her2-negative invasive ductal carcinoma, with minimal nodal disease. Compared to the BCS group, TM patients were younger, had larger tumors, had higher nomogram scores predicting additional axillary disease and were more likely to receive chemotherapy. Ninety-four percent of the BCS cohort and 5 % of the TM cohort received adjuvant radiotherapy. At a median follow-up of 57.8 months, the 4-year local, regional and distant failure rates were 1.7, 1.2 and 0.7 % in the TM group and 1.4, 1.0 and 3.7 % in the BCS group. The 4-year disease-free and overall survival rates were 94.8 and 97.8 % in the TM group and 90.1 and 92.6 % in the BCS group., Conclusions: Early-stage breast cancer patients with minimal sentinel node disease experience excellent outcomes without ALND, whether they undergo BCS or TM.

Sentinel lymph node biopsy has allowed improved staging of the axilla with reduced morbidity in breast cancer patients. However, as with any new technology there are questions as to how to best implement the technique into clinical practice. Changes in the staging system for breast cancer have incorporated sentinel lymph node biopsy findings, resulting in questions as to how to manage the remainder of the axilla when there is low volume disease in the sentinel lymph nodes. The use of the sentinel lymph node to predict additional positive nodes and to direct surgical management of the axilla and adjuvant systemic and radiation therapy is reviewed.

Overexpression of P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP), and several other proteins has been associated with development of multidrug resistance by cancer cells, which represents a significant obstacle to successful treatment by chemotherapy. We had previously demonstrated that a single noncytotoxic dose of mitomycin C (MMC), carboplatin, or one of several other DNA cross-linking agents suppressed mRNA expression of the mdr1 gene coding for Pgp, leading to a subsequent suppression of Pgp protein levels and a concomitant decrease in drug efflux. Pretreatment with MMC led to a 5- to 10-fold decrease in the ED50 for cell killing by a subsequent agent such as the Pgp substrate, doxorubicin, but did not affect killing by the non-Pgp substrate, cisplatin. In this study, we report that MMC and carboplatin each significantly suppressed Pgp protein levels in human MDA-MB-435 cells xenografted as solid tumors into the lateral mammary fat pads of female nude mice, with a similar time course as had previously been observed in cell culture. Pretreatment of mice with MMC or carboplatin 48-72 h prior to receiving either doxorubicin or paclitaxel caused a significantly greater reduction in tumor growth rate compared to either agent alone or the combination given simultaneously. These data suggest that a combination chemotherapy regimen consisting of a DNA cross-linking agent given to modulate the MDR phenotype, followed by a second cytotoxic agent, may be an effective treatment for human patients with de novo or late stage acquired multidrug-resistant malignancies.

This work is concerned with a morphometric analysis of 23 breast fibroadenomas subdivided into four histological subgroups from purely pericanalicular to purely endocanalicular forms. The volume fractions (Vv) of the lumina and the total volume: epithelial surface ratios (Sv) showed a significant (P less than 0.001) correlation (r = + 0.64). In addition, the Vv and Sv series did not correlate with any of the histological subgroups. The data reported in this work suggest that the ductal epithelium proliferates in fibroadenomas, and that the subtypes are not related to the epithelial growth.