Abstract
This cohort study examines associations between type of breast cancer surgery and changes in frailty status among US women aged 70 years or older with early-stage breast cancer.
The aging US population and increasing numbers of older adults with breast cancer highlight the need to determine how age-related syndromes, such as frailty, alter cancer outcomes and how cancer treatments change aging trajectories. Most older patients with breast cancer present with ductal carcinoma in situ (DCIS) or early-stage, hormone receptor (HR)–positive disease.1 Among them, chemotherapy has minimal potential benefits, leaving locoregional therapy (surgery and radiation therapy [RT]) as the mainstay of treatment. This cohort study assessed the association between surgery type and change in frailty status in older patients with early-stage breast cancer undergoing locoregional therapy.
Methods
We identified women aged 65 years or older diagnosed with DCIS or stage I HR-positive and ERBB2–positive breast cancer in Surveillance, Epidemiology, and End Results (SEER) Medicare data who underwent locoregional therapy between January 2010 and October 2015. Exclusion factors included unknown surgery type, HR status, noncontinuous Medicare Parts A and B coverage 1 year before and after diagnosis, chemotherapy use, prior breast cancer, or breast cancer diagnosed by death certificate. Worsening frailty status was defined as a decrement of 0.03 or greater in Kim and colleagues’ claims-based frailty index2 from diagnosis to 1 year after diagnosis, a change associated with greater mortality risk and cost of care (Dae Kim, MD, MPH, email communication, July 2022). The exposure of interest was lumpectomy vs mastectomy. Covariates included age, race and ethnicity (as coded in SEER), frailty status at diagnosis, zip code median income level, and urban or rural status. This study followed STROBE reporting guidelines. The Mass General Brigham institutional review board deemed this study exempt and waived informed because data were deidentified.
We performed multivariate generalized linear mixed regression models after adjusting for risk factors chosen a priori. Analyses were conducted using SAS, version 9.4. Data were analyzed from March to June 2022.
Results
Among 31 084 women (median age, 73 years [IQR, 69-70 years]), 22.6% underwent mastectomy, 77.4% underwent lumpectomy, and 21.4% experienced worsening frailty (Table 1). At diagnosis, 55.6% had robustness, 40.3% had prefrailty, 3.8% had mild frailty, and 0.3% had moderate to severe frailty. After adjusting for covariates, women who underwent mastectomy vs lumpectomy (odds ratio [OR], 1.31; 95% CI, 1.23-1.39), had robustness vs moderate to severe frailty at baseline (OR, 6.12; 95% CI, 2.80-13.35), were 75 years or older vs 65 to 69 years (75-79: OR, 1.21 [95% CI, 1.12-1.31]; 80-84: OR, 1.53 [95% CI, 1.40-1.66]; ≥85: OR, 1.94 [95% CI, 1.75-2.13]), or were African American/Black vs non-Hispanic White (OR, 1.12; 95% CI, 1.01-1.24) had a higher likelihood of worsening frailty (Table 2).
Table 1. Patient Characteristics of Women Older Than 70 Years With DCIS or T1N0 HR-Positive and ERBB2-Positive Breast Cancer Who Underwent Locoregional Therapy.
| Characteristic | Patients, No. (%) | ||
|---|---|---|---|
| Total | Breast conservation | Mastectomy | |
| Overall, No./total No. | 31 084 (100) | 24 069 (77.4) | 7015 (22.6) |
| Baseline frailty status | |||
| Robust | 17 298 (55.6) | 13 465 (55.9) | 3833 (54.6) |
| Prefrailty | 12 540 (40.3) | 9682 (40.2) | 2858 (40.7) |
| Mild frailty | 1166 (3.8) | 872 (3.6) | 294 (4.2) |
| Moderate to severe frailty | 80 (0.3) | 50 (0.2) | 30 (0.4) |
| Change in frailty status | |||
| Worsening | 6646 (21.4) | 4908 (20.4) | 1738 (24.8) |
| No change or improvement | 24 438 (78.6) | 19 161 (79.6) | 5277 (75.2) |
| Age, y | |||
| 65-69 | 7815 (25.1) | 5966 (24.8) | 1848 (26.4) |
| 70-74 | 9474 (30.5) | 7271 (30.2) | 2203 (31.4) |
| 75-79 | 6879 (22.1) | 5409 (22.5) | 1470 (21.0) |
| 80-84 | 4356 (14.0) | 3404 (14.1) | 952 (13.6) |
| ≥85 | 2560 (8.2) | 2019 (8.4) | 541 (7.7) |
| Race and ethnicity | |||
| African American/Black | 2107 (6.8) | 1495 (6.2) | 612 (8.7) |
| Hispanic/Latinx White | 1441 (4.6) | 1114 (4.6) | 327 (4.7) |
| Non-Hispanic/Latinx White | 25 632 (82.5) | 20 083 (83.4) | 5549 (79.1) |
| Other or unknowna | 1904 (6.1) | 1377 (5.8) | 527 (7.5) |
| Income by zip code, quartile | |||
| 1 | 4229 (13.6) | 2998 (12.5) | 1231 (17.6) |
| 2 | 5987 (19.3) | 4441 (18.5) | 1546 (22.0) |
| 3 | 8080 (26.0) | 6282 (26.1) | 1798 (25.6) |
| 4 | 12 788 (41.1) | 10 348 (42.9) | 2440 (34.8) |
| Urban or rural status by zip code | |||
| Urban | 15 737 (50.6) | 12 364 (51.4) | 3373 (48.1) |
| Rural | 3127 (10.1) | 2223 (9.2) | 904 (12.9) |
| Unknown | 12 220 (39.3) | 9482 (39.4) | 2738 (39.0) |
| Treatment type | |||
| Lumpectomy alone | 4390 (14.1) | 4390 (18.2) | NA |
| Lumpectomy and RT | 4140 (13.3) | 4140 (17.2) | NA |
| Lumpectomy and axillary surgery | 3918 (12.6) | 3918 (16.3) | NA |
| Lumpectomy, axillary surgery, and RT | 11 621 (37.4) | 11 621 (48.3) | NA |
| Mastectomy alone | 846 (2.7) | 0 | 846 (12.1) |
| Mastectomy and axillary surgery | 6169 (19.9) | 0 | 6169 (87.9) |
| Tumor stage | |||
| DCIS | 9962 (32.1) | 7665 (31.9) | 2297 (32.7) |
| T1 | 21 122 (67.9) | 16 404 (68.1) | 4718 (67.3) |
Abbreviations: DCIS, ductal carcinoma in situ; HR, hormone receptor; NA, not applicable; RT, radiotherapy.
Other race and ethnicity includes patients coded as American Indian, Asian Indian, Chamorran, Chinese, Fiji Islander, Filipino, Guamanian, Hawaiian, Hmong Kampuchean, Japanese, Korean, Laotian, Melanesian, Micronesian, New Guinean, Pakistani, Polynesian, Samoan, Tahitian, Thai, Tongan, Vietnamese, other Asian not otherwise specified, Pacific Islander not otherwise specified, or other in the Surveillance, Epidemiology, and End Results data.
Table 2. Multivariable Analysis of Worsening Frailty Status in Women Older Than 70 Years With DCIS or T1N0 HR-Positive and ERBB2-Positive Disease.
| Variable | Odds ratio (95% CI) |
|---|---|
| Treatment type | |
| Mastectomy-containing regimen | 1.31 (1.23-1.39) |
| Lumpectomy-containing regimen | 1 [Reference] |
| Baseline frailty status | |
| Robust | 6.12 (2.80-13.35) |
| Prefrailty | 3.45 (1.59-7.55) |
| Mild frailty | 2.51 (1.14-5.60) |
| Moderate to severe frailty | 1 [Reference] |
| Age, y | |
| 65-69 | 1 [Reference] |
| 70-74 | 1.03 (0.96-1.10) |
| 75-79 | 1.21 (1.12-1.31) |
| 80-84 | 1.53 (1.40-1.66) |
| ≥85 | 1.94 (1.75-2.13) |
| Race and ethnicity | |
| African American/Black | 1.12 (1.01-1.24) |
| Hispanic/Latinx White | 1.01 (0.89-1.14) |
| Non-Hispanic/Latinx White | 1 [Reference] |
| Othera | 0.90 (0.80-1.00) |
| Unknown | 0.70 (0.49-1.00) |
| Income by zip code, quartile | |
| 1 | 1 [Reference] |
| 2 | 0.89 (0.81-0.97) |
| 3 | 0.94 (0.86-1.03) |
| 4 | 0.87 (0.80-0.94) |
| Urban or rural status | |
| Urban | 1 [Reference] |
| Rural | 0.98 (0.89-1.07) |
| Unknown | 1.04 (0.99-1.10) |
Abbreviations: DCIS, ductal carcinoma in situ; HR, hormone receptor.
Other race and ethnicity includes patients coded as American Indian, Asian Indian, Chamorran, Chinese, Fiji Islander, Filipino, Guamanian, Hawaiian, Hmong Kampuchean, Japanese, Korean, Laotian, Melanesian, Micronesian, New Guinean, Pakistani, Polynesian, Samoan, Tahitian, Thai, Tongan, Vietnamese, other Asian not otherwise specified, Pacific Islander not otherwise specified, or other in the Surveillance, Epidemiology, and End Results data.
Discussion
We found that 4.1% of women aged 65 years or older with DCIS stage I breast cancer had frailty at diagnosis, but 21.4% experienced clinically significant decline. Those who had robustness at diagnosis and those who underwent mastectomy had significantly higher odds of decline. Tailoring locoregional therapy intensity in this population is important as clinical trial data have shown equivalent survival between lumpectomy and mastectomy3 and that RT and axillary surgery can be safely omitted in older adults with early-stage HR-positive disease.4 That women in the robust category were more likely to develop frailty after locoregional therapy suggests that thoughtful treatment decisions should be undertaken in all older women, not simply those who have frailty at diagnosis.
Limitations include reliance on coding in the SEER Medicare data, possible ceiling effects with respect to frailty status at diagnosis, and lack of a gold standard for clinically significant frailty. Previous studies have documented lasting declines in functional status after surgery in older patients with breast cancer,5 but breast cancer treatment has not been implicated in worsening frailty to date.6 Given the substantial proportion of women experiencing worsening frailty and the significant difference by breast surgery type, frailty status as a cancer therapy outcome should be further explored.
Data Sharing Statement
References
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Supplementary Materials
Data Sharing Statement