Katharine Yao

Repeat Surgery After Breast Conservation for the Treatment of Stage 0 to II Breast Carcinoma A Report From the National Cancer Data Base, 2004-2010

IMPORTANCE Although complete excision of breast cancer is accepted as the best means to reduce local recurrence and thereby improve survival, there is currently no standard margin width for breast conservation surgery. As a result, significant variability exists in the number of additional operations or repeat surgeries patients undergo to establish tumor-negative margins. OBJECTIVE To determine the patient, tumor, and facility factors that influence repeat surgery rates in US patients undergoing breast conservation surgery. DESIGN, SETTING, AND PATIENTS Patients diagnosed as having breast cancer at a Commission on Cancer accredited center from January 1, 2004, through December 31, 2010, and identified via the National Cancer Data Base, a large observational database, were included in the analysis. A total of 316,114 patients with stage 0 to II breast cancer who underwent initial breast conservation surgery were studied. Patients who were neoadjuvantly treated or whose conditions were diagnosed by excisional biopsy were excluded. MAIN OUTCOMES AND MEASURES Patient, tumor, and facility factors associated with repeat surgeries. RESULTS A total of 241,597 patients (76.4%) underwent a single lumpectomy, whereas 74,517 (23.6%) underwent at least 1 additional operation, of whom 46,250 (62.1%) underwent a completion lumpectomy and 28,267 (37.9%) underwent a mastectomy. The proportion of patients undergoing repeat surgery decreased slightly during the study period from 25.4% to 22.7% (P < .001). Independent predictors of repeat surgeries were age, race, insurance status, comorbidities, histologic subtype, estrogen receptor status, pathologic tumor size, node status, tumor grade, facility type and location, and volume of breast cancer cases. Age was inversely associated with repeat surgery, decreasing from 38.5% in patients 18 to 29 years old to 16.5% in those older than 80 years (P < .001). In contrast, larger tumor size was linearly associated with a higher repeat surgery rate (P < .001). Repeat surgeries were most common at facilities located in the Northeast region (26.5%) compared with facilities in the Mountain region, where only 18.4% of patients underwent repeat surgery (P < .001). Academic or research facilities had a 26.0% repeat surgery rate compared with a rate of 22.4% at community facilities (P < .001). CONCLUSIONS AND RELEVANCE Approximately one-fourth of all patients who undergo initial breast conservation surgery for breast cancer will have a subsequent operative intervention. The rate of repeat surgeries varies by patient, tumor, and facility factors and has decreased slightly during the past 6 years.

Have We Expanded the Equitable Delivery of Postmastectomy Breast Reconstruction in the New Millennium? Evidence from the National Cancer Data Base

BACKGROUND Studies examining patterns of cancer care before 2000 have shown underuse of postmastectomy breast reconstruction as well as racial and socioeconomic disparities in its delivery. These findings prompted legislation designed to broaden use at the turn of the millennium. However, little is known about trends in these findings over the past decade. STUDY DESIGN Patients who underwent mastectomy for stage 0 to III breast cancer between 1998 and 2007 (n = 452,903) were studied using the National Cancer Data Base to evaluate trends in the receipt of immediate and early delayed breast reconstruction. Those who underwent mastectomy between 1998 and 2000 (n = 150,177) and between 2005 and 2007 (n = 123,518) were compared using logistic regression to identify factors influencing the use of breast reconstruction and how they changed over time. RESULTS The use of postmastectomy breast reconstruction increased from 13% to 26% from 1998 to 2007. This increase was statistically significant in almost all patient subsets. Independent factors associated with breast reconstruction included age less than 50 years old; higher census-derived household income; private or managed care insurance; non-African American race; and treatment in an academic hospital setting. Treatment in an academic hospital and higher income became stronger predictors of breast reconstruction over the study period, while age became less of a predictor. CONCLUSIONS Although the use of breast reconstruction has increased from 1998 to 2007, it is still underused among many patient populations. Furthermore, racial and socioeconomic disparities in its delivery have persisted or widened. Additional effort is necessary to broaden the use of breast reconstruction and to ensure equitable access to it.

Notch-1 and Notch-4 Receptors as Prognostic Markers in Breast Cancer

Background: Studies looking at immunohistochemical (IHC) staining of Notch receptors in breast cancer and correlation with known prognostic factors are sparse. Methods: IHC staining for nuclear, cytoplasmic, and membrane Notch-1 (N1), Notch-4 (N4), and Jagged-1 (JAG1) was performed and correlated with known prognostic factors. Results: Of 48 breast cancers, 36 (67%) were invasive, mean age was 50 years (range 43-86 years), 37 (77%) were estrogen receptor (ERα) positive, and 13 (27%) node positive. There was significantly more marked N1 membranous staining in ERα-positive tumors (P < .05). On univariate analysis, cytoplasmic N1 was significantly correlated with node status and tumor grade (P < .05); both cytoplasmic and membranous N4 significantly correlated with Ki67 (P < .05); and membranous JAG1 significantly correlated with Ki67 (P < .05). On multivariate analysis, only cytoplasmic N1 significantly correlated with node status. Conclusion: IHC of Notch markers is feasible and correlates with known prognostic factors consistent with a biological role of Notch signaling in breast cancer progression.

Contralateral Prophylactic Mastectomy Provides No Survival Benefit in Young Women with Estrogen Receptor-Negative Breast Cancer

BackgroundSeveral 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.MethodsWe 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.ResultsA 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.ConclusionsCPM 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.

Contralateral Prophylactic Mastectomy (CPM) Consensus Statement from the American Society of Breast Surgeons: Data on CPM Outcomes and Risks.

The American Society of Breast Surgeons (ASBrS) endorses the American Board of Internal Medicine’s Choosing Wisely campaign statement: “Don’t routinely perform a double mastectomy in patients who have a single breast with cancer.”1 However, women with a newly diagnosed unilateral breast cancer are increasingly opting for bilateral mastectomy. This has been seen in patients who are candidates for breast conservation who elect mastectomy as well as those requiring mastectomy for their index breast cancer.2 National rates of contralateral prophylactic mastectomy (CPM) in the United States have been increasing and this trend is continuing.2–4

Advanced age is a predictor of 30-day complications after autologous but not implant-based postmastectomy breast reconstruction

Background: Older breast cancer patients undergo postmastectomy breast reconstruction infrequently, in part because of a perception of increased surgical risk. This study sought to investigate the effects of age on perioperative complications after postmastectomy breast reconstruction. Methods: The American College of Surgeons National Surgery Quality Improvement Program Participant Use Files from 2005 to 2012 were used to identify women with breast cancer who underwent unilateral mastectomy alone or with immediate reconstruction. Thirty-day complication rates were compared between younger (<65 years) and older (≥65 years) women after implant-based reconstruction, autologous reconstruction, or mastectomy alone. Linear and logistic regression models were used to control for differences in comorbidities and age. Results: A total of 40,769 patients were studied, of whom 15,093 (37 percent) were aged 65 years or older. Breast reconstruction was performed in 39.5 percent of younger and 10.7 percent of older women. The attributable risks of breast reconstruction, manifested by longer hospital stays (p < 0.001), more frequent complications (p < 0.001), and more reoperations (p < 0.001), were similar in older and younger women. There were no differences in the adjusted complication rates between older and younger patients undergoing implant-based reconstruction. However, older women undergoing autologous reconstruction were more likely to suffer venous thromboembolism (OR, 3.67; p = 0.02). Conclusions: The perioperative risks attributable to breast reconstruction are similar in older and younger women. Older patients should be counseled that their age does not confer an increased risk of complications after implant-based breast reconstruction. However, age is an independent risk factor for venous thromboembolism after autologous reconstruction. Special attention should be paid to venous thromboembolism prophylaxis in this group. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Impact of the American College of Surgeons Oncology Group Z0011 Randomized Trial on the Number of Axillary Nodes Removed for Patients with Early-Stage Breast Cancer

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 Z0011s 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.

Variation in Contralateral Prophylactic Mastectomy Rates According to Racial Groups in Young Women with Breast Cancer, 1998 to 2011: A Report from the National Cancer Data Base

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.

The quality‐of‐life benefits of breast reconstruction do not diminish with age

Older women rarely receive post‐mastectomy breast reconstruction (PMBR). While there is a perception that PMBR is less beneficial in this age group, quality‐of‐life (QOL) data related to PMBR in older women remain scarce.

Contralateral prophylactic mastectomy: current perspectives

There has been an increasing trend in the use of contralateral prophylactic mastectomy (CPM) in the United States among women diagnosed with unilateral breast cancer, particularly young women. Approximately one-third of women <40 years old are undergoing CPM in the US. Most studies have shown that the CPM trend is mainly patient-driven, which reflects a changing environment for newly diagnosed breast cancer patients. The most common reason that women choose CPM is based on misperceptions about CPM’s effect on survival and overestimation of their contralateral breast cancer (CBC) risk. No prospective studies have shown survival benefit to CPM, and the CBC rate for most women is low at 10 years. Fear of recurrence is also a big driver of CPM decisions. Nonetheless, studies have shown that women are mostly satisfied with undergoing CPM, but complications and subsequent surgeries with reconstruction have been associated with dissatisfaction with CPM. Studies on surgeon’s perspectives on CPM are sparse but show that the most common reasons surgeons discuss CPM with patients is because of a suspicious family history or for a patient who is a confirmed BRCA mutation carrier. Studies on the cost–effectiveness of CPM have been conflicting and are highly dependent on patient’s quality of life after CPM. Most recent guidelines for CPM are contradictory. Future areas of research include the development of interventions to better inform patients about CPM, modification of the guidelines to form a more consistent statement, longer term studies on CBC risk and CPM’s effect on survival, and prospective studies that track the psychosocial effects of CPM on body image and sexuality.