Abstract
Background:
For average-risk women with unilateral breast cancer, contralateral prophylactic mastectomy (CPM) offers no survival benefit and contributes to increased costs and patient harm. Despite recommendations from professional societies against CPM, utilization of this service is increasing, partly due to patients’ desire for breast symmetry when undergoing mastectomy. Most women with small tumors are candidates for breast conserving surgery (BCS) and could avoid CPM. We describe CPM utilization in women with small, unilateral tumors and identify determinants of possible overuse.
Methods:
Using the National Cancer Database (NCDB), we identified women with unilateral, T1 breast cancer. We evaluated utilization of BCS, unilateral mastectomy (UM), and CPM and assessed patient, tumor, and facility factors associated with CPM.
Results:
Of 765,487 women with small, unilateral breast cancer, 69% underwent BCS and 31% chose mastectomy. Of 176,673 women ≥70 years, 75% underwent BCS and 25% chose mastectomy. CPM rates in both cohorts have increased since 2006. Decreased adjuvant radiotherapy in older women was associated with increased BCS rates. Patient factors (younger age, white race, private insurance, and breast reconstruction), tumor factors (lobular histology, higher grade, and HER2 positive/ER negative status), and facility factors (type and geographic location) were associated with increased CPM rates compared to UM in multivariable models.
Conclusion:
Most women with small unilateral breast cancer are candidates for BCS, yet one-third elects to undergo a mastectomy, of which a rising percentage opts for CPM. Tailoring de-implementation strategies to factors influencing treatment may help reduce CPM utilization and associated financial toxicity, pain, and disability.
Keywords: de-implementation, bilateral mastectomy, contralateral prophylactic mastectomy, breast conserving surgery
INTRODUCTION
For average-risk women with unilateral breast cancer, contralateral prophylactic mastectomy (CPM) does not offer a survival benefit and contributes to financial toxicity and avoidable patient harm.1,2 To improve patient and provider understanding of the indications for bilateral mastectomy in the treatment of unilateral cancer, the Society of Surgical Oncology (SSO) has published several position statements on prophylactic (risk-reducing) mastectomy, dating back to 1993 and most recently in 2017.3 The American Society of Breast Surgeons (ASBrS) has also made an official recommendation against routinely performing a double mastectomy in patients who have a single breast with cancer as part of the Choosing Wisely® campaign in 2016.4,5 To date, the Choosing Wisely® campaign is the most notable initiative aimed at the de-implementation, or discontinuation, of unnecessary health care interventions, like CPM in average-risk women with unilateral cancer. Despite recent guidelines and de-implementation efforts, CPM rates continue to rise nationwide with estimates ranging from 10–13% of all breast cancer procedures and 28–30% of all mastectomy cases.6 More troubling, this trend specifically has been observed in patients with early-stage breast cancers that have excellent prognoses with breast conserving therapy and often include older women who are the most vulnerable to the risks associated with CPM and the least likely to derive oncologic benefit.7
Women with unilateral, small tumors (<20 mm) are often candidates for breast conserving surgery (BCS), but for unclear reasons may choose to undergo unilateral mastectomy which can escalate to CPM. Previous authors have hypothesized that concerns regarding asymmetry from unilateral mastectomy drive utilization of CPM with bilateral reconstruction for symmetry.8,9 In women with small tumors, BCS not only mitigates the issue of breast asymmetry but is also associated with fewer surgical complications and costs compared to unilateral mastectomy or CPM.10 Studies show patients may also elect to undergo mastectomy in order to avoid the radiotherapy that may be recommended after BCS;11,12 however, for women over 70 years with hormone-receptor positive (HR+) breast cancer, adjuvant radiotherapy may be omitted.13 To our knowledge, no prior study has evaluated CPM utilization trends in a separate cohort of women ≥70 years old with unilateral breast cancer. Given unilateral mastectomy often escalates to CPM, the initial escalation in treatment from BCS to unilateral mastectomy represents an intervenable decision point with an opportunity for patient risk-reduction. Recognizing there are likely multi-level factors influencing treatment decisions, further research is needed to understand why early-stage breast cancer patients with unilateral, small (T1) tumors, especially older patients, choose mastectomy over BCS.14
To address the paucity of data on circumstances in which surgical care escalates from BCS to unilateral mastectomy and subsequently CPM, we sought to describe utilization patterns of these three procedures in women with small unilateral breast cancer. We additionally evaluated treatment patterns of women ≥70 years old with early-stage cancer given their age-specific treatment guideline to omit adjuvant radiotherapy. Our aim is to identify patient, tumor, and facility-level factors potentially contributing to the use of mastectomy, as opposed to BCS, to inform future strategies aimed at the de-implementation of CPM and the associated financial toxicity and harms experienced by women receiving CPM.
METHODS
Data source
The National Cancer Database (NCDB) is a joint program of the Commission on Cancer (CoC) of the American College of Surgeons and the American Cancer Society.15 Since 1989, NCDB has gathered more than 34 million records from more than 1,500 hospital cancer registries across the United States and includes data on patient demographics, cancer staging, tumor histological characteristics, types of treatment administered, and outcomes.16 This study uses only de-identified data from NCDB and is therefore not regulated by the University of Michigan institutional review board.
Study population
Using NCDB, we identified women diagnosed with unilateral breast cancer from 2006 to 2016. Women were included if they had American Joint Committee on Cancer (AJCC) clinical stage T1 N0 M0 breast cancer including both invasive and in situ disease. Patients were excluded if pathologic tumor size was greater than 20 mm, information on tumor size was missing, or tumor grade was undifferentiated (grade 4). They must have received all or part of their care at the reporting hospital. We excluded women who had received neoadjuvant therapy, were diagnosed through an excisional biopsy, or who had an unspecified or unknown type of surgery. CPM was defined as bilateral mastectomy performed for unilateral breast cancer. The sample was further limited to create a cohort of older women with HR+ invasive breast cancer who would be eligible for post-BCS radiotherapy omission based on National Comprehensive Cancer Network (NCCN) guidelines.17 Therefore, in theory, the decision to undergo mastectomy versus BCS in these women should not be dependent on patient eligibility or preference to avoid radiotherapy. For this cohort, women were included if they were ≥70 years old and had estrogen receptor or progesterone receptor positive invasive breast cancer. Older patients with in situ disease were excluded, as current national guidelines for radiotherapy omission only apply to women ≥70 years old with invasive breast cancer.
Independent variables
For this study, we examined patient, tumor, and facility-level factors. Patient factors included age, race, insurance status, year of diagnosis, comorbidity index, and receipt of breast reconstruction. Race was classified by the US census data categories: White/Caucasian, Black/African American, Asian, Native American/Hawaiian/Alaskan, other, or unknown. Insurance status was categorized into private insurance, government insurance (Medicaid or Medicare), no insurance, or unknown. Comorbidity index was based on Charlson-Deyo score of 0 to 3+. Breast reconstruction data is part of the NCDB Site-Specific Surgery Codes and is reported as “yes” or “no” without specification as to whether it is immediate or delayed reconstruction. BRCA mutation status or other high-risk clinical features were not included because NCDB does not provide this information. Tumor factors included tumor size, behavior, grade, hormone receptor subtype, and HER2 receptor status. Tumor histology was classified as ductal, lobular, mixed ductal and lobular histology, or other. Facility-level factors examined included facility type, facility region, and annual hospital breast cancer volume. Facilities were categorized as one of four CoC accreditation designations that take into account the range of services offered, number of annual cases, and participation in clinical research and resident training: community cancer program, comprehensive community cancer program, academic/research program, or integrated network cancer program. Facilities were categorized regionally based upon the state of the reporting facility: New England (CT, MA, ME, NH, RI, VT), Middle Atlantic (NJ, NY, PA), South Atlantic (DC, DE, FL, GA, MD, NC, SC, VA, WV), East North Central (IL, IN, MI, OH, WI), East South Central (AL, KY, MS, TN), West North Central (IA, KS, MN, MO, ND, NE, SD), West South Central (AR, LA, OK, TX), Mountain (AZ, CO, ID, MT, NM, NV, UT, WY), and Pacific (AK, CA, HI, OR, WA). Annual facility breast cancer volume was calculated based on the total number of breast cancer cases seen by the facility during the study period.
Dependent Variables and Statistical analysis
The primary outcome was the type of surgical treatment received. Secondary outcomes included receipt of post-BCS radiotherapy and receipt of breast reconstruction. To determine the effect of patient, tumor, and facility characteristics on breast cancer surgery receipt, we first performed bivariate analyses with Pearson’s chi-squared and Kruskal-Willis tests as appropriate. Statistically significant factors were incorporated into multi-level mixed-effects logistic regression models. Two separate models were performed to estimate two outcomes, the receipt of mastectomy (CPM and unilateral) compared to BCS and the receipt of CPM compared to unilateral mastectomy. For each model, we included patient, tumor, and facility characteristics as fixed effects. The facility identifier number was included as a random-effects parameter to account for clustering within each facility. Due to the lack of available information on HER2 receptor status prior to 2010, only patients treated from 2010–2016 were included in the univariable and multivariable analyses. This was in contrast to the time period from 2006–2016, which was used to evaluate trends over time. Analyses were performed with STATA version 16 (StataCorp, College Station, TX) and SAS Software 9.4 (SAS Institute, Cary, NC). All statistical tests were two-sided with a p-value of <0.05 considered statistically significant.
RESULTS
Study population
A total of 765,487 cases met eligibility criteria for this study. Women with clinically node negative, unilateral T1 breast cancers completed the following procedures: BCS (69%), unilateral mastectomy (22%), and CPM (9%) (Table 1). A total of 176,673 cases met the eligibility criteria when restricting the cohort of subjects to women ≥70 years old with HR+ invasive breast cancer. Women over ≥70 years old completed the following procedures: BCS (75%), unilateral mastectomy (22%), and CPM (3%) (Table 2).
Table 1.
Patient demographics of women with clinically node negative, unilateral T1 breast cancer by surgery type.
| Lumpectomy n=527,792 n (%) |
Unilateral Mastectomy n=165,688 n (%) |
Contralateral Prophylactic Mastectomy n=72,007 n (%) |
p-value | |
|---|---|---|---|---|
| Patient | ||||
| Age (mean ± SD) | 63.7 ± 11.8 | 62.6 ± 12.8 | 54.4 ± 11.3 | <0.01 |
| Race | <0.01 | |||
| White | 455,252 (69.2) | 138,384 (21.0) | 64,325 (9.8) | |
| Black | 48,144 (68.9) | 17,172 (24.6) | 4,545 (6.5) | |
| Native American | 1,141 (65.0) | 460 (26.2) | 155 (8.8) | |
| Asian | 15,565 (63.1) | 7,281 (29.3) | 1,891 (7.7) | |
| Other | 3,4040 (67.4) | 1,164 (23.1) | 482 (9.5) | |
| Insurance | <0.01 | |||
| Not Insured | 5,982 (66.4) | 2,323 (25.8) | 708 (7.86) | |
| Private | 262,700 (66.2) | 81,643 (20.6) | 52,366 (13.20) | |
| Medicaid | 20,341 (65.0) | 8,019 (25.6) | 2,939 (9.39) | |
| Medicare | 229,517 (73.0) | 70,549 (22.4) | 14,526 (4.62) | |
| Other | 4,374 (64.3) | 1,543 (22.7) | 891 (13.09) | |
| Charlson Score | <0.01 | |||
| 0 | 438,272 (69.3) | 132,584 (21.0) | 61,541 (9.7) | |
| 1 | 71,852 (67.4) | 25,946 (24.4) | 8,751 (8.2) | |
| 2 | 13,488 (66.7) | 5,377 (26.6) | 1,351 (6.7) | |
| 3+ | 4,180 (66.1) | 1,781 (28.2) | 364 (5.8) | |
| Breast Reconstruction | <0.01 | |||
| No | N/A | 117,521 (70.9) | 27,263 (37.9) | |
| Yes | N/A | 48,167 (29.1) | 44,744 (62.1) | |
| Tumor | ||||
| Tumor Size (mean ± SD) | 10.4 ± 5.1 | 11.0 ± 5.5 | 10.8 ± 5.5 | <0.01 |
| Behavior | <0.01 | |||
| In situ | 98,836 (71.7) | 25,833 (18.8) | 13,095 (9.5) | |
| Invasive | 428,956 (68.3) | 139,855 (22.3) | 58,912 (9.4) | |
| Grade | <0.01 | |||
| 1 | 157,548 (73.8) | 39,408 (18.5) | 16,428 (7.7) | |
| 2 | 225,917 (68.6) | 73,059 (22.2) | 30,389 (9.2) | |
| 3 | 107,089 (63.9) | 40,904 (24.4) | 19,578 (11.7) | |
| Histology | <0.01 | |||
| Ductal | 407,399 (69.2) | 126,568 (21.5) | 54,917 (9.3) | |
| Lobular | 38,036 (65.9) | 13,381 (23.2) | 6,316 (10.9) | |
| Mixed ductal/lobular | 23,962 (64.0) | 9,591 (25.6) | 3,914 (10.5) | |
| Other | 58,395 (71.7) | 16,148 (19.8) | 6,860 (8.4) | |
| ER status | <0.01 | |||
| Negative | 58,963 (61.5) | 25,358 (26.4) | 11,604 (12.1) | |
| Positive | 454,768 (70.2) | 134,984 (20.8) | 58,152 (9.0) | |
| Borderline | 311 (61.5) | 145 (28.7) | 40 (9.9) | |
| HER2 Status* | <0.01 | |||
| Negative | 272,662 (70.8) | 75,299 (19.6) | 37,298 (9.7) | |
| Positive | 21,468 (57.8) | 10,621 (28.6) | 5,064 (13.6) | |
| Borderline | 5,969 (66.9) | 2,020 (22.6) | 939 (10.5) | |
| Facility | ||||
| Annual Volume (mean ± SD) | 247.8 ± 224.4 | 252.4± 235.0 | 274.8± 236.7 | <0.01 |
| Facility Type | <0.01 | |||
| Comm Cancer Prog | 46,529 (72.0) | 14,272 (22.1) | 3,803 (5.9) | |
| Compreh Comm | 244,559 (69.7) | 74,768 (21.3) | 31,327 (8.9) | |
| Academic | 151,418 (68.8) | 48,590 (22.1) | 20,003 (9.1) | |
| Integrated Net | 78,424 (69.6) | 23,297 (20.7) | 10,991 (9.8) | |
| Facility Location | <0.01 | |||
| New England | 39,548 (78.0) | 8,300 (16.4) | 2,838 (5.6) | |
| Mid Atlantic | 85,837 (72.9) | 23,098 (19.6) | 8,785 (7.5) | |
| South Atlantic | 117,613 (68.9) | 37,770 (22.1) | 15,422 (9.0) | |
| E Nor Central | 95,306 (71.3) | 28,749 (21.5) | 9,605 (7.2) | |
| E South Central | 26,996 (60.0) | 12,008 (26.78) | 5,988 (13.3) | |
| W Nor Central | 39,790 (67.3) | 12,802 (21.7) | 6,530 (11.0) | |
| W South Central | 31,811 (63.5) | 12,630 (25.2) | 5,650 (11.3) | |
| Mountain | 22,808 (68.5) | 6,650 (20.0) | 3,860 (11.6) | |
| Pacific | 61,221 (69.9) | 18,920 (21.6) | 7,446 (8.5) | |
HER2 status available for years 2010–2016 only
Table 2.
Patient demographics of women ≥70 years old with clinically node negative, HR+ unilateral T1 invasive breast cancer by surgery type.
| Lumpectomy n=131,867 n (%) |
Unilateral Mastectomy n=39,532 n (%) |
Contralateral Prophylactic Mastectomy n=5,274 n (%) |
p-value | |
|---|---|---|---|---|
| Patient | ||||
| Age (mean ± SD) | 77.1 ± 5.4 | 77.3 ± 5.3 | 74.8 ± 4.3 | <0.01 |
| Race | <0.01 | |||
| White | 119,803 (75.0) | 35,097 (22.0) | 4,929 (3.1) | |
| Black | 8,203 (72.0) | 2,998 (26.3) | 200 (1.8) | |
| Native American | 195 (67.5) | 85 (29.4) | 9 (3.1) | |
| Asian | 2,259 (68.6) | 955 (29.0) | 80 (2.4) | |
| Other | 576 (77.2) | 147 (19.7) | 23 (3.1) | |
| Insurance | <0.01 | |||
| Not Insured | 310 (69.4) | 119 (26.6) | 18 (4.0) | |
| Private | 14,065 (75.6) | 3,964 (21.3) | 569 (3.1) | |
| Medicaid | 1,360 (74.0) | 443 (24.1) | 35 (1.9) | |
| Medicare | 114,497 (74.5) | 34,551 (22.5) | 4,574 (3.0) | |
| Other | 490 (73.8) | 144 (21.7) | 30 (4.5) | |
| Charlson Score | <0.01 | |||
| 0 | 102,197 (75.9) | 28,538 (21.2) | 3,902 (2.9) | |
| 1 | 22,866 (71.0) | 8,236 (25.6) | 1,095 (3.4) | |
| 2 | 5,070 (69.2) | 2,051 (28.0) | 205 (2.8) | |
| 3+ | 1,734 (69.0) | 707 (28.1) | 72 (2.9) | |
| Breast Reconstruction | <0.01 | |||
| No | N/A | 36,503 (92.3) | 4,069 (77.2) | |
| Yes | N/A | 3,029 (7.7) | 1,205 (22.9) | |
| Tumor | ||||
| Tumor Size (mean ± SD) | 10.7 ± 4.7 | 11.7 ± 5.1 | 11.3 ± 5.0 | <0.01 |
| Grade | <0.01 | |||
| 1 | 50,639 (78.0) | 12,579 (19.4) | 1,743 (2.7) | |
| 2 | 62,935 (73.7) | 19,792 (23.2) | 2,643 (3.1) | |
| 3 | 12,840 (68.6) | 5,270 (28.2) | 614 (3.3) | |
| Histology | <0.01 | |||
| Ductal | 102,378 (75.5) | 29,469 (21.7) | 3,782 (2.8) | |
| Lobular | 12,630 (70.0) | 4,612 (25.6) | 797 (4.4) | |
| Mixed ductal/lobular | 7,034 (69.0) | 2,772 (27.2) | 385 (3.8) | |
| Other | 9,825 (76.7) | 2,679 (20.9) | 310 (2.4) | |
| HER2 Status* | <0.01 | |||
| Negative | 87,816 (77.2) | 22,239 (19.6) | 3,714 (3.3) | |
| Positive | 4,286 (66.9) | 1,857 (29.0) | 262 (4.1) | |
| Borderline | 1,762 (72.0) | 596 (24.3) | 91 (3.7) | |
| Facility | ||||
| Annual Volume (mean ± SD) | 234.0 ± 206.2 | 211.7 ± 185.5 | 216.5 ± 168.6 | <0.01 |
| Facility Type | <0.01 | |||
| Comm Cancer Prog | 12,799 (71.4) | 4,649 (25.9) | 481 (2.7) | |
| Compreh Comm | 63,940 (73.6) | 20,102 (23.1) | 2,873 (3.3) | |
| Academic | 35,045 (77.6) | 8,991 (19.9) | 1,103 (2.4) | |
| Integrated Net | 20,083 (75.3) | 5,790 (21.7) | 817 (3.1) | |
| Facility Location | <0.01 | |||
| New England | 10,411 (82.8) | 1,989 (15.8) | 177 (1.4) | |
| Mid Atlantic | 21,942 (79.7) | 5,053 (18.4) | 530 (1.9) | |
| South Atlantic | 29,414 (74.3) | 8,903 (22.5) | 1,276 (3.2) | |
| E Nor Central | 24,346 (75.3) | 7,287 (22.5) | 715 (2.2) | |
| E South Central | 6,404 (63.1) | 3,259 (32.1) | 483 (4.8) | |
| W Nor Central | 10,530 (70.8) | 3,738 (25.1) | 604 (4.1) | |
| W South Central | 7,266 (67.0) | 3,105 (28.7) | 468 (4.3) | |
| Mountain | 5,648 (74.5) | 1,620 (21.4) | 314 (4.1) | |
| Pacific | 15,906 (75.1) | 4,578 (21.6) | 707 (3.3) | |
HER2 status available for years 2010–2016 only
Trends in breast surgery over time
For the total cohort, actual unilateral mastectomy rates decreased from 25% in 2006 to 18% in 2016 (Figure 1). There was a corresponding increase in actual CPM rates from 6% in 2006 to 9% in 2016 with a peak of 11% in 2013, representing a relative decrease of 18% from 2013 to 2016. Actual rates of BCS were comparatively stable over time and modestly increased from 70% in 2006 to 73% in 2016. Of the patients who received a mastectomy, the absolute percentage who received CPM increased from 19% in 2006 to 34% in 2016. These trends were consistent after adjusting for patient, tumor, and facility-level characteristics on multivariable models. More recent year of surgery was independently associated with decreased odds of receiving mastectomy compared to BCS and increased odds of receiving CPM compared to unilateral mastectomy (Tables 3 and 4).
Figure 1.
Trends in breast conserving surgery, unilateral mastectomy, and contralateral prophylactic mastectomy in women with clinically node negative, unilateral T1 breast cancer from 2006–2016.
Table 3.
Adjusted odds ratios (OR) with 95% confidence interval (CI) from multivariable logistic regression analysis predicting the odds of receiving mastectomy (unilateral mastectomy or contralateral prophylactic mastectomy) compared to breast conserving surgery for women diagnosed with clinically node negative, unilateral T1 breast cancer from 2010–2016.
| All women n = 537,733 OR (95% CI) |
Women ≥70 years old with HR+ invasive breast cancer n = 125,924 OR (95% CI) |
|
|---|---|---|
| Year | ||
| 2010 | ref | ref |
| 2011 | 1.01 (0.99, 1.03) | 0.94 (0.91, 0.98) |
| 2012 | 1.00 (0.97, 1.02) | 0.88 (0.84, 0.93) |
| 2013 | 0.96 (0.94, 0.99) | 0.81 (0.78, 0.85) |
| 2014 | 0.91 (0.89, 0.93) | 0.74 (0.70, 0.77) |
| 2015 | 0.84 (0.82, 0.85) | 0.65 (0.62, 0.68) |
| 2016 | 0.75 (0.73, 0.77) | 0.56 (0.53, 0.59) |
| Patient | ||
| Age (years) | 0.97 (0.97, 0.97) | 0.99 (0.98, 0.99) |
| Race | ||
| White | ref | ref |
| Black | 0.86 (0.84, 0.88) | 1.10 (1.04, 1.17) |
| Native American | 1.33 (1.28, 1.39) | 1.60 (1.44,1.78) |
| Asian | 1.01 (0.89, 1.13) | 1.38 (1.07, 1.78) |
| Other | 0.95 (0.87, 1.03) | 1.02 (0.83, 1.26) |
| Insurance | ||
| Private | ref | ref |
| Not Insured | 0.87 (0.81, 0.93) | 1.11 (0.85, 1.46) |
| Medicaid | 1.01 (0.97, 1.05) | 1.02 (0.88, 1.18) |
| Medicare | 1.11 (1.08, 1.13) | 1.05 (1.00, 1.10) |
| Other | 1.06 (0.99, 1.14) | 1.02 (0.81, 1.28) |
| Charlson Score | ||
| 0 | ref | ref |
| 1 | 1.15 (1.13, 1.17) | 1.18 (1.14, 1.22) |
| 2 | 1.25 (1.20,1.31) | 1.31 (1.22, 1.40) |
| 3+ | 1.33 (1.24, 1.43) | 1.38 (1.24, 1.54) |
| Tumor | ||
| Tumor Size (mm) | 1.01 (1.01, 1.02) | 1.04 (1.03, 1.04) |
| Invasive Behavior | ||
| In situ | ref | --- |
| Invasive | 1.40 (1.33, 1.47) | --- |
| Grade | ||
| 1 | ref | ref |
| 2 | 1.25 (1.23, 1.27) | 1.22 (1.19, 1.26) |
| 3 | 1.33 (1.29, 1.36) | 1.46 (1.39, 1.53) |
| Histology | ||
| Ductal | ref | ref |
| Lobular | 1.46 (1.42, 1.50) | 1.34 (1.28, 1.40) |
| Mixed ductal/lobular | 1.45 (1.40, 1.49) | 1.46 (1.38, 1.55) |
| Other | 1.00 (0.97, 1.03) | 1.01 (0.96, 1.08) |
| ER status | ||
| Positive | ref | --- |
| Negative | 1.27 (1.24, 1.30) | --- |
| Borderline | 1.28 (0.84, 1.97) | --- |
| HER2 Status | ||
| Negative | ref | ref |
| Positive | 1.54 (1.50, 1.58) | 1.48 (1.39, 1.57) |
| Borderline | 1.21 (1.15, 1.27) | 1.24 (1.12, 1.36) |
| Facility | ||
| Annual Volume | 1.00 (0.95, 1.05) | 0.82 (0.78, 0.87) |
| Facility Type | ||
| Academic | ref | ref |
| Comm Cancer Prog | 0.89 (0.79, 1.00) | 0.98 (0.86, 1.13) |
| Compreh Comm | 0.94 (0.87, 1.02) | 1.06 (0.97, 1.17) |
| Integrated Net | 0.98 (0.88, 1.08) | 0.98 (0.87, 1.11) |
| Facility Location | ||
| New England | ref | ref |
| Mid Atlantic | 1.31 (1.15, 1.50) | 1.36 (1.16, 1.60) |
| South Atlantic | 1.67 (1.48, 1.90) | 1.78 (1.53, 2.06) |
| E Nor Central | 1.46 (1.28, 1.65) | 1.61 (1.38, 1.86) |
| E South Central | 2.47 (2.12, 2.88) | 2.95 (2.46, 3.53) |
| W Nor Central | 1.80 (1.55, 2.09) | 2.05 (1.72, 2.43) |
| W South Central | 2.08 (1.79, 2.40) | 2.41 (2.03, 2.87) |
| Mountain | 1.67 (1.41, 1.98) | 1.76 (1.43, 2.15) |
| Pacific | 1.60 (1.39,1.83) | 1.66 (1.41, 1.95) |
Table 4.
Adjusted odds ratios (OR) with 95% confidence interval (CI) from multivariable logistic regression analysis predicting the odds of receiving contralateral prophylactic mastectomy compared to unilateral mastectomy for women diagnosed with clinically node negative, unilateral T1 breast cancer from 2010–2016.
| All women n = 163,408 OR (95% CI) |
Women ≥70 years old with HR+ invasive breast cancer n = 29,771 OR (95% CI) |
|
|---|---|---|
| Year | ||
| 2010 | ref | ref |
| 2011 | 1.10 (1.06, 1.14) | 1.10 (0.99, 1.21) |
| 2012 | 1.23 (1.17, 1.29) | 1.25 (1.10, 1.43) |
| 2013 | 1.35 (1.29, 1.42) | 1.42 (1.25, 1.62) |
| 2014 | 1.44 (1.38, 1.51) | 1.55 (1.37, 1.75) |
| 2015 | 1.46 (1.40, 1.53) | 1.54 (1.37, 1.72) |
| 2016 | 1.38 (1.30, 1.45) | 1.33 (1.15, 1.54) |
| Patient | ||
| Age (years) | 0.95 (0.95, 0.96) | 0.92 (0.91, 0.93) |
| Race | ||
| White | ref | ref |
| Black | 0.55 (0.52, 0.58) | 0.41 (0.34, 0.50) |
| Native American | 0.49 (0.45, 0.53) | 0.54 (0.40, 0.73) |
| Asian | 0.62 (0.49, 0.79) | 0.66 (0.34, 1.31) |
| Other | 0.69 (0.58, 0.82) | 1.00 (0.58, 1.73) |
| Insurance | ||
| Private | ref | ref |
| Not Insured | 0.60 (0.52, 0.69) | 0.87 (0.44, 1.74) |
| Medicaid | 0.74 (0.69, 0.79) | 0.54 (0.34, 0.86) |
| Medicare | 0.93 (0.89, 0.97) | 0.97 (0.86, 1.10) |
| Other | 1.05 (0.92, 1.19) | 1.25 (0.74, 2.11) |
| Charlson Score | ||
| 0 | ref | ref |
| 1 | 1.06 (1.02, 1.10) | 1.03 (0.94, 1.13) |
| 2 | 0.99 (0.90, 1.08) | 0.81 (0.68, 0.97) |
| 3+ | 0.92 (0.79, 1.07) | 0.88 (0.66, 1.18) |
| Breast Reconstruction | ||
| No | ref | ref |
| Yes | 2.73 (2.64, 2.82) | 2.57 (2.33, 2.83) |
| Tumor | ||
| Tumor Size (mm) | 1.00 (1.00, 1.00) | 0.99 (0.98, 0.998) |
| Invasive Behavior | ||
| In situ | ref | --- |
| Invasive | 1.10 (1.00, 1.22) | --- |
| Grade | ||
| 1 | ref | ref |
| 2 | 1.02 (0.98, 1.05) | 1.01 (0.93, 1.10) |
| 3 | 1.10 (1.05, 1.15) | 0.99 (0.88, 1.13) |
| Histology | ||
| Ductal | ref | ref |
| Lobular | 1.20 (1.15, 1.26) | 1.39 (1.25, 1.55) |
| Mixed ductal/lobular | 0.97 (0.91, 1.03) | 1.08 (0.94, 1.25) |
| Other | 0.97 (0.91, 1.04) | 0.88 (0.75, 1.04) |
| ER status | ||
| Positive | ref | --- |
| Negative | 1.22 (1.16, 1.27) | --- |
| Borderline | 0.81 (0.35, 1.85) | --- |
| HER2 Status | ||
| Negative | ref | ref |
| Positive | 0.87 (0.83, 0.91) | 0.92 (0.79, 1.07) |
| Borderline | 0.97 (0.88, 1.07) | 0.91 (0.71, 1.17) |
| Facility | ||
| Annual Volume | 0.98 (0.92, 1.05) | 0.94 (0.85, 1.03) |
| Facility Type | ||
| Academic | ref | ref |
| Comm Cancer Prog | 0.98 (0.84, 1.14) | 0.89 (0.70, 1.13) |
| Compreh Comm | 1.19 (1.07, 1.32) | 1.16 (1.00, 1.35) |
| Integrated Net | 1.26 (1.11, 1.44) | 1.25 (1.03, 1.52) |
| Facility Location | ||
| New England | ref | ref |
| Mid Atlantic | 1.14 (0.95, 1.37) | 1.10 (0.83, 1.47) |
| South Atlantic | 1.38 (1.17, 1.63) | 1.58 (1.21, 2.07) |
| E Nor Central | 1.13 (0.95, 1.34) | 1.14 (0.87, 1.51) |
| E South Central | 1.96 (1.60, 2.39) | 1.71 (1.26, 2.33) |
| W Nor Central | 1.81 (1.49, 2.20) | 1.88 (1.40, 2.54) |
| W South Central | 1.69 (1.39, 2.05) | 1.80 (1.33, 2.44) |
| Mountain | 1.85 (1.49, 2.31) | 1.97 (1.41, 2.76) |
| Pacific | 1.37 (1.14, 1.64) | 1.67 (1.25, 2.23) |
When limiting the analysis to the older cohort, actual unilateral mastectomy rates decreased from 28% in 2006 to 16% in 2016 (Figure 2). There was a corresponding increase in actual CPM rates from 2% in 2006 to 3% in 2016 with a peak of 4% in 2015. Actual rates of BCS increased from 71% in 2006 to 81% in 2016. This trend of increasing rates of BCS compared to mastectomy over time parallels a decrease in actual rates of adjuvant radiotherapy administration from 69% in 2006 to 56% in 2016, suggesting that the recommendation allowing for post-BCS radiotherapy omission in these women may have contributed to a decrease in the percent of women electing for mastectomy. Rates of radiotherapy in women <70 years old with invasive breast cancer remained stable from 2006 to 2016 (Figure 3).
Figure 2.
Trends in breast conserving surgery, unilateral mastectomy, and contralateral prophylactic mastectomy in women ≥70 years old with clinically node negative, HR+ unilateral T1 invasive breast cancer from 2006–2016.
Figure 3.
Trends in adjuvant radiotherapy in breast conserving surgery patients with clinically node negative, unilateral T1 invasive breast cancer from 2006–2016. Cohort of women ≥70 years old limited to patients with HR+ breast cancer.
Multi-level factors associated with preference for mastectomy compared to breast conserving surgery
On univariable and multivariable analysis, patient factors associated with significantly increased odds of mastectomy compared to BCS were younger age and increased comorbidity scores. Black women were less likely to undergo mastectomy and Native American women were more likely to undergo mastectomy when compared to white women. Compared to patients with private insurance, patients who were uninsured had decreased odds of mastectomy, while Medicare patients had increased odds of mastectomy. When evaluating the cohort of women ≥70 years old with HR+ invasive breast cancer, patient characteristics associated with significantly increased odds of mastectomy compared to BCS were younger age, minority racial status (black, Native American, or Asian race), and increased comorbidity scores. There were no differences based on insurance status.
Tumor factors associated with significantly increased odds of mastectomy compared to BCS in both cohorts of women were increased tumor size, increased grade, lobular or mixed histology (compared to ductal histology), ER negative hormone-receptor-status (compared to ER positive), and positive or borderline HER2 receptor status (compared to HER2 negative). In the overall cohort, invasive behavior (compared to in situ) was also associated with increased odds of mastectomy compared to BCS.
Facility-level factors associated with differential rates of mastectomy compared to BCS were facility type and geographic location. Patients who received surgery at community cancer programs or facilities located in New England had lower odds of receiving mastectomy compared to other hospitals. There was no association between odds of receiving mastectomy and hospital breast cancer volume. When evaluating the cohort of women ≥70 years old with HR+ invasive breast cancer, facility characteristics associated with decreased odds of receiving mastectomy compared to BCS were increased hospital breast cancer volume and geographic location in New England. There were no differences based on facility type for the older cohort (Tables 1–3).
Multi-level factors associated with preference for CPM compared to unilateral mastectomy
On bivariate and multivariable analysis, patient factors associated with significantly increased odds of CPM compared to unilateral mastectomy were younger age, white race, and private insurance. There was no difference in CPM rates based on comorbidity scores. The receipt of breast reconstruction was the strongest predictor for undergoing CPM. Twenty-nine percent of unilateral mastectomy patients received breast reconstruction compared to 38% of CPM patients. Similar findings were observed when evaluating the cohort of women ≥70 years old with HR+ invasive breast cancer, with the exception of insurance status. Women insured by Medicaid had significantly lower rates of CPM compared to other insurance types; there was no difference between patients with private insurance compared to those with Medicare. Among older patients, breast reconstruction was still the strongest factor associated with undergoing CPM compared to unilateral mastectomy; 8% of unilateral mastectomy patients received breast reconstruction compared to 23% of CPM patients.
Tumor factors associated with significantly increased odds of CPM compared to unilateral mastectomy were increased grade, lobular histology (compared to ductal histology), ER negative hormone-receptor-status (compared to ER positive), and HER2 receptor positive status (compared to HER2 negative). There was no difference based on tumor size or invasive compared to in situ behavior. Tumor characteristics associated with increased CPM rates in older women with HR+ invasive breast cancer were lobular histology and smaller tumor size. There were no differences based on grade or HER2 receptor status.
For facility-level factors, patients treated at comprehensive community and integrated network cancer programs had increased odds of receiving CPM compared to other facility types. Hospitals in New England, the Mid-Atlantic, and East North Central regions had significantly lower odds of CPM compared to other geographic regions. There were no differences based on facility breast cancer volume. Similar findings were observed in the cohort of women ≥70 years old (Tables 1, 2, and 4).
DISCUSSION
In this nationwide study assessing trends and multi-level factors associated with surgical treatment of low-risk breast cancer, we report increasing rates of CPM in women who would be eligible for breast conservation. We identify specific patient, tumor, and facility level-characteristics associated with CPM utilization overall and limited to women ≥70 years. Our results align with others in the literature demonstrating that CPM rates are increasing while unilateral mastectomy rates are decreasing. However, our study is unique in that it specifically assesses women with small T1 tumors, which allows us to better understand breast cancer surgery escalation through identification of the multi-level factors influencing treatment decisions in women who are eligible for BCS but undergo mastectomy. Furthermore, to our knowledge, our study is the first to specifically evaluate CPM utilization patterns in a separate cohort of women over 70 years old who can possibly omit adjuvant radiotherapy. Nearly all women ≥70 years with small T1 tumors should be eligible for BCS and yet our data shows that a quarter of women are choosing mastectomy. This cohort of older patients represents a group of women who are choosing more surgery despite a lack of survival benefit.
A common justification for the increasing number of women undergoing CPM has been the wider availability of breast reconstruction and the desire for improved symmetry associated with bilateral mastectomies and breast reconstruction compared to unilateral mastectomy with or without reconstruction.18,19 While this may be a reasonable strategy for patients requiring mastectomy due to large tumor size or other contraindications to BCS, our study specifically evaluated only patients with small T1 tumors. Although nearly all of the patients with these small tumors were likely candidates for BCS, approximately 20% underwent unilateral mastectomy and 10% received bilateral procedures. This finding is meaningful due to the increased morbidity and costs associated with CPM and unilateral mastectomy (particularly when paired with breast reconstruction) compared to BCS and the associated lack of survival benefit.10
Despite the overall increase in CPM rates since 2006, a modest decrease in rates from 2013 to 2016 suggests the feasibility of reducing CPM through interventions that target specific factors associated with persistent CPM utilization. We show that variations in breast surgery trends are attributable to patient, tumor, and facility-level factors. One notable patient factor associated with higher rates of mastectomy compared to BCS is increased comorbidity scores. This may indicate that patients with multiple comorbidities are unwilling or unable to complete radiation therapy given treatment-specific toxicities or associated burdens of adjuvant radiotherapy (e.g. daily travel burden). Therefore, women with higher comorbidity scores may undergo mastectomy instead of BCS because mastectomy may be perceived as the less burdensome surgical option. Interestingly, this finding is also true in women ≥70 years old with HR+ breast cancer, a cohort in which 25% received a mastectomy. The high rate of mastectomy in older women with small, unilateral tumors is surprising because NCCN guidelines have evolved since 2004 to allow for omission of radiotherapy after BCS in older women based on randomized trials demonstrating no improvements in long-term survival rates.20,21 This may suggest that many older women are not counseled preoperatively about their option to omit adjuvant radiotherapy. While mastectomy may be a reasonable option over BCS in some younger women who are unable to complete adjuvant radiotherapy or have a strong desire to avoid it, this is not the case for women over 70 years.
The introduction of guidelines allowing for adjuvant radiotherapy omission in women ≥70 years old with HR+, T1 invasive breast cancer and the dissemination of the long-term follow-up results from the CALGB trial probably contributes to the significant change over time in patterns of breast surgery seen in our results.20 Unlike in the overall cohort in which BCS rates are relatively stable over time, in older women BCS rates are increasing. This trend directly overlaps a decrease in unilateral mastectomy and corresponding decrease in adjuvant radiotherapy rates in women ≥70 years old with HR+ invasive breast cancer. Although CPM utilization only modestly increased in women over 70 years between 2006 and 2016, given these women represent up to a third of all new breast cancer patients, a rate of 3% equates to non-trivial numbers of women undergoing CPM in place of BCS. This highlights an imperative to target CPM for complete de-implementation, especially because women ≥70 years old are unlikely to benefit from CPM and are at particularly high risk of postoperative complications.22 Our data demonstrate a decreasing rate of adjuvant radiotherapy in women ≥70 years, however more than 50% of women over 70 years, who may be eligible for omission, continue to receive radiation therapy after BCS. A lack of shared decision-making regarding the acceptability of radiation omission may influence a patient’s decision to undergo mastectomy as opposed to BCS, suggesting that in order to reduce mastectomy in older patients, the potential overuse of adjuvant radiotherapy should be targeted for de-implementation as well. Providers should encourage patients with small T1 tumors who are candidates for adjuvant radiotherapy omission to both omit radiotherapy and undergo BCS, emphasizing the equivalent survival rates of BCS, unilateral mastectomy, and CPM, as well as the lack of survival benefit associated with adjuvant radiotherapy.
Of the patients who receive a mastectomy, the most significant factor that appears to contribute to increasing CPM rates is the receipt of breast reconstruction. Sixty-two percent of CPM patients received breast reconstruction compared to 29% of unilateral mastectomy patients. Both of these percentages are higher than previously reported in the literature likely because of the wider availability of breast reconstruction in recent years.23,24 While breast reconstruction after mastectomy offers notable benefits to patients including improved quality of life, satisfaction with appearance, and reduced physical limitations, the availability of breast reconstruction should not drive overutilization of unilateral mastectomy or CPM when BCS is feasible.25 Other patient factors that appear to drive high rates of CPM compared to unilateral mastectomy include young age, white race, and private insurance. This supports the common observation that CPM is frequently driven by patient preferences, which has been attributed to fear of recurrence, anxiety over continued surveillance, and misinformation over the potential risks and benefits.8,26
Tumor-level factors that may contribute to high mastectomy rates are tumor subtypes with perceived or known higher risk of recurrence. Overall, patients with higher grade tumors, invasive tumors (compared to in situ), increased tumor size, ER negative status, HER2 positive status, and lobular or mixed histology have significantly increased odds of receiving a mastectomy compared to BCS. Similar trends are observed in the cohort of older women. However, while some tumor subtypes such has HER2 positive status and lobular histology are associated with increased risk of recurrence, this risk has not been shown to be mitigated by more extensive surgery, including unilateral and bilateral mastectomy compared to BCS.27 As a result, current guidelines do not recommend that these biological factors should influence surgery type.28 A potential strategy to decrease the likelihood that patients pursue a unilateral or bilateral mastectomy out of a misguided fear of recurrence is improved patient-provider risk communication. A survey of breast cancer survivors found that women with unilateral breast cancer substantially overestimate their risk of developing a contralateral breast cancer and on average believe that their 10-year risk is around 30%.29 At the same time, providers are also known to overestimate the benefits and underestimate the risks associated with most medical treatments.30 As a result, alternate methods of providing patients with accurate risk estimations are necessary. As an example, pictographs have been shown to improve risk communication compared to standard written or numerical formats and can be adapted to patients’ risk factors.31
Finally, facility-level factors that may be associated with differential rates of BCS, unilateral mastectomy, and CPM for patients with small, unilateral tumors include the facility type and location. In comparison to other facility types, community cancer programs had significantly lower odds of mastectomy versus BCS, while comprehensive community and integrated network cancer programs had significantly higher odds of CPM compared to unilateral mastectomy. Overall, New England was the geographic region with the highest rates of BCS, while the East South Central region had the highest odds of both unilateral and bilateral mastectomy. There was no difference in practice patterns based on breast cancer volume at each facility. Overall, these differences may reflect variations in guideline dissemination (e.g. the acceptability of radiotherapy omission in older women after BCS), entrenched practice patterns, variable availability of breast reconstruction, or patient preferences based on regional culture.
There are several limitations to this study due to its retrospective nature. Importantly, NCDB is not a population-based registry. However, it currently captures more than 70% of all new cancer cases in the country, which allows for the generalizability of these conclusions. Additionally, NCDB does not provide information on BRCA mutation status or other high-risk features for which risk-reducing CPM is appropriate and indicated. However, prior work has demonstrated that the vast majority of patients who pursue CPM do not have major genetic or familial risk factors for contralateral disease and therefore these disease-specific risk factors are unlikely to be driving the noted CPM trends.32 In the setting of recent multigene panel-based testing identifying non-BRCA1/2 genes associated with moderate or high breast cancer risk, pathogenic variations associated with bilateral breast cancer are shown to occur at low frequencies in patients with breast cancer receiving germline genetic testing.33 Furthermore, for women over 70 years old, the survival benefit that may be provided by CPM in the setting of a pathogenic mutation or other high-risk features increasing a patient’s odds of developing bilateral breast cancer is unlikely to be achieved. Finally, the findings in this study of multi-level factors that may contribute to varied surgical procedure utilization for small, unilateral breast cancer are based on associations that would require further evaluation for determination of causal effects.
CONCLUSIONS
Persistently high rates of CPM in women with clinically node negative, unilateral T1 breast cancer suggest that opportunities remain for reducing potential surgical overtreatment in this low-risk cancer population. Although the majority of these patients are candidates for BCS, one-third elect to undergo mastectomy, of which a rising percentage opts for CPM. Slight decreases in CPM rates in recent years suggest an opportunity to develop strategies to reduce CPM rates in low-risk patients by targeting specific patient, tumor, and facility level-factors associated with CPM utilization. As a result of our study’s data, to discourage the use of CPM we recommend increasing patient-facing education pertaining to the risks associated with CPM, improving patient-provider communication about cancer recurrence with low-risk tumors, tailoring breast cancer treatment recommendations for older women using age-specific guidelines, and expanding de-implementation efforts to target supply-side drivers of CPM based on local practice patterns. Tailoring de-implementation strategies to factors influencing treatment may help reduce CPM rates and associated patient morbidity.
Disclosure:
Dr. Dossett is supported by a grant from the Agency for Healthcare Research and Quality (AHRQ) K08 HS026030-02. Dr. Wang is supported by a grant from the National Cancer Institute T32 CA009672. Dr. Berlin receives funding from the Department of Veterans Affairs supporting his role as a National Clinician Scholar. Ms. Baskin is supported by scholarship funding from the University of Michigan Rogel Cancer Center.
Footnotes
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