ABSTRACT
Purpose
Breast cancer patients with higher body mass index (BMI) experience worsened outcomes, though a knowledge gap remains regarding whether treatment differs by BMI. This study examined how BMI was associated with breast cancer treatment among Iowans.
Methods
Iowa Cancer Registry data were linked with state driver's license data to calculate BMI. Among those with stage I–III cancers, we assessed differences in breast cancer surgery (BCS), reconstruction, chemotherapy, hormone therapy, and radiation therapy between BMI categories using logistic regression models. We restricted analyses of reconstruction to individuals who received surgery, and hormone therapy to hormone receptor‐positive (HR+) patients. We used multinomial models to assess the type of BCS received.
Results
Nearly all of the 18,115 included patients received surgery (97%), 63% received chemotherapy, 79% of HR+ patients received hormone therapy, and 63% received radiation therapy. Patients with higher BMI had decreased odds for reconstruction (BMI 25.0–29.9 kg/m2 aOR = 0.81, 95% CI: 0.71, 0.93; BMI 30.0–34.9 kg/m2 aOR = 0.62, 95% CI: 0.51, 0.74; BMI 35.0+ kg/m2 aOR = 0.44, 95% CI: 0.34, 0.57), and, among patients with HR+, increased odds of hormone therapy (BMI 25.0–29.9 kg/m2 aOR = 1.14, 95% CI: 1.03, 1.26; BMI 30.0–34.9 kg/m2 aOR = 1.15, 95% CI: 1.01, 1.30; BMI 35.0+ kg/m2 aOR = 1.22, 95% CI: 1.04, 1.42). Patients with higher BMI were more likely to receive lumpectomy than unilateral/bilateral mastectomy.
Discussion
These findings suggest breast cancer treatment differences exist for patients with higher BMI. Future research is warranted to understand mechanisms behind differences, both to ensure breast cancer patients with higher BMIs receive adequate and appropriate cancer care and to understand whether treatment differences contribute to observed survival differences.
Keywords: body mass index, breast cancer, treatment
1. Introduction
Breast cancer is the most incident cancer [1], and second leading cause of cancer death in women [2]. However, with early diagnosis and adequate treatment, long‐term survival is achievable, as demonstrated by 91.2% 5‐year survival [1]. Higher weight patients are at greater risk for developing post‐menopausal breast cancer and experience lower survival than those of lower weight [3, 4, 5]. Unfortunately, mechanisms underlying the impact of body size on breast cancer incidence, recurrence, and survival have not been comprehensively elucidated, impeding efforts to address this disparity. Associations of post‐menopausal breast cancer incidence and survival with higher body weight (defined clinically as “clinical obesity”) [6] are often attributed to differences in estrogen metabolism and efficacy of anti‐estrogen medication, particularly for estrogen‐receptor positive cases [7, 8, 9]. However, higher weight patients with non‐estrogen sensitive breast cancer subtypes also experience worse outcomes [10], suggesting other factors may contribute to the relationship between body size and breast cancer disease progression and survival.
Lower breast cancer survival among higher weight women may be related to differences in access to and utilization of healthcare services across the cancer continuum [11, 12], which has been less thoroughly investigated than underlying biology. For example, higher weight women have lower utilization of screening for early detection of cancers [13, 14, 15, 16], which could explain an increased likelihood for later‐stage diagnoses [17, 18]. Further, higher weight women may receive lower‐than‐guideline‐recommended doses of chemotherapy drugs, resulting in worse outcomes [19]. However, a gap remains regarding whether differences in treatment occur by body size. It is important to better understand how weight and weight status are related to breast cancer treatment to inform future clinical practice and develop interventions to reduce weight‐based disparities in breast cancer outcomes.
To address this research gap, we analyzed Iowa Cancer Registry data to assess whether and how body size, operationalized using body mass index (BMI), was associated with receipt of breast cancer treatment among Iowa breast cancer patients. Specifically, we assessed whether BMI was associated with receipt of first‐course breast cancer surgery, chemotherapy, radiation therapy, and hormone therapy. Adding to the sparse body of literature and in line with previous survey research [20], we hypothesized that there would be differences in receipt of treatment by BMI.
2. Methods
2.1. Language and Terminology
Language can be othering, causing harm and contributing to stigma against those with larger bodies. While there has been a move in recent years toward person‐first language [21, 22], others have argued this language contributes to the ongoing stigmatization of those in larger bodies [23]. Further, although the medical establishment has positioned the term “obesity” as a neutral term, it is often not interpreted as such by higher weight people [24, 25, 26]. While there is no one preferred term among the people that this terminology affects, in this manuscript we adhere to recommendations regarding the use of weight neutral terms wherever possible [23]. We do use terms including “obesity” where this reflects use of terms in the primary literature.
We use BMI to categorize weight of patients relative to height. While self‐reported BMI is known to be less accurate than clinical measures, these data show good agreement with BMI as recorded in medical records [27]. Though we may miss some individuals who underestimated their weight, the specificity of those classified as having “obesity” using these criteria is likely to be high. We recognize that BMI is a flawed metric that does not well represent either adiposity or health, especially in the context of clinical utility at the patient level [28]. Indeed, because of its historical harm and use for racist exclusion [29], the American Medical Association does not recommend BMI for sole use in diagnosing “obesity” [30]. However, because this metric remains commonly used in clinical practice for decision‐making, we determined it suitable for use in this study.
2.2. Ethics and Data Availability
This study was given expedited ethics approval by the University of Iowa Institutional Review Board. Data are available through application to the Iowa Cancer Registry.
2.3. Data Source and Study Population
Data on demographic and clinical characteristics were obtained from the Iowa Cancer Registry for female breast cancer patients diagnosed among Iowa residents between January 1, 2010 and December 31, 2020. Breast cancer patients eligible for inclusion were women aged 18 years or older with a first primary, histologically confirmed, malignant stage I–III breast cancer diagnosis. Patients excluded from the analytic dataset were those with concurrent tumors within 3 months, with histology codes 9050–9055, 9140, and 9590–9992, diagnosed via autopsy or death certificate, pathologic diagnosis only, and only treated in the Veterans Affair system, Mayo Clinic Health system, or gathered from state data exchange.
We linked Iowa Cancer Registry data with state driver's license data to obtain information on patient weight and height, which were used to calculate BMI as weight in kilograms divided by height in meters squared. Height and weight information was taken from the most recent driver's license for each individual. Individuals were only included in this study if their date of driver's license issue was within 8 years of (i.e., prior to) the date of diagnosis. Further, individuals whose date of license issuance was after diagnosis were excluded from the study.
2.4. Measures
The independent variable used in this study was BMI, a measure of weight relative to height [31]. We categorized BMI as 18.5–24.9, 25.0–29.9, 30.0–34.9, and greater than/equal to 35.0 kg/m2, which reflect current clinical obesity categorizations [32]. As we were primarily interested in differences in breast cancer treatment between BMI categories, particularly for those in the higher BMI categories, we did not include patients with a BMI reflecting underweight (i.e., < 18.5 kg/m2).
Outcomes were receipt of breast cancer surgery, reconstruction, chemotherapy, hormone therapy, and radiation therapy; identified using data from the Iowa Cancer Registry. Receipt of surgery, chemotherapy, hormone therapy, and radiation therapy were all categorized as yes (received), recommended but not given, contraindicated/not planned for first‐line therapy/patient died before beginning treatment, and not given for an unknown reason. Surgery type was restricted to those who received surgery, and was categorized as lumpectomy, unilateral mastectomy, or bilateral mastectomy, and by receipt of reconstruction. It should be noted that the completeness of radiation and chemotherapy variables in SEER Program registries is known to be low: one study comparing SEER to Medicare data observed 68% and 80% sensitivity for chemotherapy and radiation (overall), respectively.16 For this reason it is not recommended for use estimating prevalence of chemotherapy or radiation services received. We include these variables in this study with the assumption that missingness of these data is non‐differential by BMI; therefore, is suitable to indicate relative receipt (e.g., ranking those with the highest % radiation received is likely to represent “truth,” even if the proportions themselves are lower than “truth”).
Covariates included age at diagnosis (< 40, 40–49, 50–59, 60–69, 70+ years), race/ethnicity (non‐Hispanic White, non‐Hispanic Black, Hispanic [any race], other/unknown), marital status (married or living with partner, unmarried, divorced/separated/widowed), insurance (private, Medicaid, Medicare, none/unknown/other), patient rurality (metropolitan, nonmetropolitan), hospital rurality (metropolitan, nonmetropolitan), year of diagnosis (2010–2015, 2016–2020), stage (I, II, III), breast cancer subtype (HR+/HER2+, HR+/HER2−, HR−/HER2+, triple negative, missing), grade (1, 2, 3/4), treatment facility type (National Cancer Institute [NCI] designated, Commission on Cancer [CoC] accredited, Critical Access Hospital, non‐CoC, unknown treating facility), percent of females with bachelor's degree or higher, median household income, and number of facilities the patients visited (0, 1, 2+). Facility type was assigned from highest designation to lowest; for example, facilities with both NCI and CoC designation were assigned NCI; facilities with both CoC and Critical Access Hospital status were assigned CoC. Area‐based social measures were determined at census tract level, according to the patient's address at time of diagnosis, except for percent of females with bachelor's degree or higher, which is measured at county level. Both continuous variables, percent of females with a bachelor's degree or higher and median household income, were dichotomized at the national median (22.8% and $57,770, respectively).
2.5. Statistical Analysis
Frequencies of demographic characteristics and receipt of treatments are presented by BMI category and compared using Chi‐square tests. Univariable and multivariable‐adjusted logistic regression models were built to assess differences between BMI categories in receipt of surgery, reconstruction (among those who had surgery), chemotherapy, hormone therapy (among HR+ patients), and radiation therapy. Variables were selected for models using backward stepwise regression, with race ultimately being forced into models for hormone therapy and radiation therapy. We built a multinomial model to assess receipt of lumpectomy (reference group), unilateral mastectomy, and bilateral mastectomy between BMI categories, among patients who received surgery. In all models, the lowest BMI category (18.5–24.9 kg/m2) was the reference category.
All analyses were conducted using SAS 9.4 software (SAS Institute, Cary, NC). p‐Values less than 0.05 were considered statistically significant.
3. Results
3.1. Descriptive Statistics
There were 18,129 breast cancer patients eligible for inclusion (Table 1). Of these, 39% had a BMI of 18.5–24.9 kg/m2, 33% had a BMI of 25.0–29.9 kg/m2, 17% had a BMI of 30.0–34.9 kg/m2, and 10% had a BMI of 35.0+ kg/m2. Nearly all patients (96%) were White, and more than half were older than 60 years of age (59%), married (64%), lived in metropolitan areas (57%), had stage I cancer (64%), HR+/HER2− subtype (74%), and were treated at metropolitan facilities (80%). Those in higher BMI groups were more likely to be older, non‐White, unmarried, more frequently covered by Medicaid and less frequently covered by private insurance, and more likely to be treated at metropolitan facilities. Higher BMI groups were less likely to live in areas with a greater‐than‐average proportion of residents with a bachelor's degree or higher, and more likely to live in a census tract with a lower‐than‐average median household income. Median time [IQR] from driver's license issuance to diagnosis was −662 days [−1200 days, −322 days].
TABLE 1.
Clinical and demographic characteristics, by body mass index (BMI), of breast cancers diagnosed 2010–2020 within the Iowa Cancer Registry.
| All | BMI 18.5–24.9 kg/m2 | BMI 25.0–29.9 kg/m2 | BMI 30.0–34.9 kg/m2 | BMI 35.0+ kg/m2 | Chi‐sq p‐value | |
|---|---|---|---|---|---|---|
| N (col %) | N (col %) | N (col %) | N (col %) | N (col %) | ||
| All | 18,115 | 7046 | 6060 | 3122 | 1887 | |
| Age at diagnosis | < 0.0001 | |||||
| < 40 | 809 (4) | 449 (6) | 220 (4) | 86 (3) | 54 (3) | |
| 40–49 | 2528 (14) | 1286 (18) | 713 (12) | 324 (10) | 205 (11) | |
| 50–59 | 4216 (23) | 1789 (25) | 1303 (22) | 669 (21) | 455 (24) | |
| 60–69 | 5196 (29) | 1729 (25) | 1790 (30) | 1015 (33) | 662 (35) | |
| 70+ | 5366 (30) | 1793 (25) | 2034 (34) | 1028 (33) | 511 (27) | |
| Race/Ethnicity | < 0.0001 | |||||
| White | 17,376 (96) | 6784 (96) | 5830 (96) | 2990 (96) | 1772 (94) | |
| Black | 292 (2) | 59 (1) | 88 (1) | 67 (2) | 78 (4) | |
| Hispanic (any race) | 197 (1) | 59 (1) | 76 (1) | 38 (1) | 24 (1) | |
| Other/unknown | 250 (1) | 144 (2) | 66 (1) | 27 (1) | 13 (1) | |
| Marital status | < 0.0001 | |||||
| Married or living with domestic partner | 11,709 (64) | 4836 (69) | 3940 (65) | 1877 (60) | 1056 (56) | |
| Single | 1771 (10) | 639 (9) | 524 (9) | 353 (11) | 255 (14) | |
| Divorced/separated/widowed | 4295 (24) | 1452 (20) | 1489 (24) | 825 (27) | 529 (28) | |
| Unknown | 340 (2) | 119 (2) | 107 (2) | 67 (2) | 47 (2) | |
| Insurance | < 0.0001 | |||||
| Private | 7644 (42) | 3435 (49) | 2378 (39) | 1136 (36) | 695 (37) | |
| Medicaid | 807 (4) | 288 (4) | 236 (4) | 156 (5) | 127 (7) | |
| Medicare | 7738 (43) | 2499 (35) | 2815 (46) | 1538 (49) | 886 (47) | |
| None/unknown/other | 1926 (11) | 824 (12) | 631 (10) | 292 (9) | 179 (9) | |
| Patient rurality | 0.19 | |||||
| Metropolitan | 10,406 (57) | 4066 (58) | 3441 (57) | 1777 (57) | 1122 (59) | |
| Nonmetropolitan | 7709 (43) | 2980 (42) | 2619 (43) | 1345 (43) | 765 (41) | |
| Year of diagnosis | < 0.0001 | |||||
| 2010–2015 | 9436 (52) | 3822 (54) | 3178 (52) | 1558 (50) | 878 (47) | |
| 2016–2020 | 8679 (48) | 3224 (46) | 2882 (48) | 1564 (50) | 1009 (53) | |
| Stage | 0.56 | |||||
| 1 | 11,599 (64) | 4479 (64) | 3921 (65) | 2002 (64) | 1197 (63) | |
| 2 | 4828 (27) | 1892 (27) | 1612 (27) | 819 (26) | 505 (27) | |
| 3 | 1688 (9) | 675 (10) | 527 (9) | 301 (10) | 185 (10) | |
| Breast subtype | 0.0002 | |||||
| HR−/HER2+ | 698 (4) | 315 (4) | 205 (3) | 99 (3) | 79 (4) | |
| HR+/HER2− | 13,348 (74) | 5035 (71) | 4533 (75) | 2359 (76) | 1421 (75) | |
| HR+/HER2+ | 1685 (9) | 692 (10) | 562 (9) | 269 (9) | 162 (9) | |
| Triple negative | 1943 (11) | 797 (11) | 620 (10) | 337 (11) | 189 (10) | |
| Missing | 441 (2) | 207 (3) | 140 (2) | 58 (2) | 36 (2) | |
| Grade | 0.19 | |||||
| 1 | 5002 (28) | 1928 (27) | 1706 (28) | 841 (27) | 527 (28) | |
| 2 | 7577 (42) | 2899 (41) | 2584 (43) | 1326 (42) | 768 (41) | |
| 3/4 | 5232 (29) | 2086 (30) | 1677 (28) | 904 (29) | 565 (30) | |
| Unknown | 304 (2) | 133 (2) | 93 (2) | 51 (2) | 27 (1) | |
| Facility type | < 0.0001 | |||||
| CAH | 1070 (6) | 399 (6) | 369 (6) | 204 (7) | 98 (5) | |
| CoC | 10,179 (56) | 3919 (56) | 3358 (55) | 1783 (57) | 1119 (59) | |
| NCI | 1693 (9) | 781 (11) | 548 (9) | 233 (7) | 131 (7) | |
| Non‐CoC | 5020 (28) | 1880 (27) | 1740 (29) | 878 (28) | 522 (28) | |
| Unknown treating facility | 154 (1) | 67 (1) | 45 (1) | 25 (1) | 17 (1) | |
| Hospital rurality | 0.004 | |||||
| Metropolitan | 14,497 (80) | 5713 (82) | 4816 (80) | 2446 (79) | 1522 (81) | |
| Nonmetropolitan | 3370 (19) | 1232 (17) | 1165 (19) | 632 (20) | 341 (18) | |
| Missing | 248 (1) | 101 (1) | 79 (1) | 45 (1) | 24 (1) | |
| Percent of females with bachelor's degree or higher | < 0.0001 | |||||
| Above median (22.8%+) | 9836 (54) | 3968 (56) | 3323 (55) | 1605 (51) | 940 (50) | |
| Below median (< 22.8%) | 8279 (46) | 3078 (44) | 2737 (45) | 1517 (49) | 947 (50) | |
| Median Household Income | < 0.0001 | |||||
| Above median ($57,770+) | 8558 (47) | 3457 (49) | 2928 (48) | 1402 (45) | 773 (41) | |
| Below median (< $57,770) | 8185 (45) | 3008 (43) | 2707 (45) | 1501 (48) | 975 (51) | |
| Missing | 1372 (8) | 582 (8) | 425 (7) | 222 (7) | 144 (8) |
3.2. Treatments Received
Nearly all patients received surgery to treat their cancer (97%). Among patients who received surgery, 60% received lumpectomy, 6% received bilateral mastectomy with reconstruction, 7% received bilateral mastectomy without reconstruction, 3% received unilateral mastectomy with reconstruction, and 22% received unilateral mastectomy without reconstruction (Table 2). The majority of patients received hormone therapy (among HR+ patients only) (79%), received radiation therapy (63%), and did not receive chemotherapy (63%); of those who received both surgery and systemic therapy, most received adjuvant systemic therapy (69%). There were 156 patients with no treatment recorded in the cancer registry.
TABLE 2.
Breast cancer treatments received, by body mass index (BMI), of breast cancers diagnosed 2010–2020 within the Iowa Cancer Registry.
| All | BMI 18.5–24.9 kg/m2 | BMI 25.0–29.9 kg/m2 | BMI 30.0–34.9 kg/m2 | BMI 35.0+ kg/m2 | |
|---|---|---|---|---|---|
| N (col %) | N (col %) | N (col %) | N (col %) | N (col %) | |
| All | 18,115 | 7046 | 6060 | 3122 | 1887 |
| Surgery | |||||
| Yes | 17,666 (97) | 6875 (98) | 5914 (98) | 3048 (97) | 1829 (97) |
| Recommended but not given | 184 (1) | 76 (1) | 61 (1) | 30 (1) | 17 (1) |
| Contraindicated/not planned first course/patient died before receiving treatment | 265 (1) | 76 (1) | 61 (1) | 44 (1) | 41 (2) |
| Extent of surgery a | |||||
| Bilateral mastectomy and reconstruction | 1144 (6) | 617 (9) | 346 (6) | 122 (4) | 59 (3) |
| Bilateral mastectomy and no reconstruction | 1275 (7) | 483 (7) | 379 (6) | 236 (8) | 177 (9) |
| Unilateral mastectomy and reconstruction | 475 (3) | 249 (4) | 132 (2) | 64 (2) | 30 (2) |
| Unilateral mastectomy and no reconstruction | 3916 (22) | 1670 (24) | 1252 (21) | 655 (21) | 339 (18) |
| Lumpectomy | 10,853 (60) | 3856 (55) | 3804 (63) | 1970 (63) | 1223 (65) |
| Other | 452 (3) | 171 (2) | 147 (2) | 75 (3) | 59 (3) |
| Sequence of surgery and systemic therapy a | |||||
| Adjuvant | 12,505 (69) | 4709 (67) | 4239 (70) | 2220 (71) | 1337 (71) |
| Neoadjuvant | 686 (4) | 300 (4) | 198 (3) | 121 (4) | 67 (4) |
| No surgical procedures and/or systemic therapy; unknown if surgery and/or systemic therapy given | 3160 (17) | 1309 (19) | 1064 (18) | 498 (16) | 289 (15) |
| Missing | 1764 (10) | 728 (10) | 559 (9) | 283 (9) | 194 (10) |
| Chemotherapy a | |||||
| Yes | 6706 (37) | 2744 (39) | 2133 (35) | 1142 (37) | 687 (36) |
| Recommended but not given | 741 (4) | 291 (4) | 272 (4) | 109 (3) | 69 (4) |
| Contraindicated/not planned first course/patient died before receiving treatment | 281 (2) | 91 (1) | 68 (1) | 70 (2) | 52 (3) |
| Not received, unknown reason | 10,387 (57) | 3920 (56) | 3587 (59) | 1801 (58) | 1079 (57) |
| Hormone therapy (among HR+ patients) a | |||||
| Yes | 12,097 (79) | 4513 (77) | 4129 (80) | 2147 (80) | 1308 (81) |
| Recommended but not given | 945 (6) | 409 (7) | 304 (6) | 145 (5) | 87 (5) |
| Contraindicated/not planned first course/patient died before receiving treatment | 82 (1) | 36 (1) | 27 (1) | 9 (< 1) | 10 (1) |
| Not received, unknown reason | 2218 (14) | 908 (15) | 731 (14) | 375 (14) | 204 (13) |
| Radiation therapy a | |||||
| Yes | 11,463 (63) | 4238 (60) | 3922 (65) | 2064 (66) | 1239 (65) |
| Recommended but not given | 743 (4) | 282 (4) | 262 (4) | 121 (4) | 79 (4) |
| Contraindicated/not planned first course/patient died before receiving treatment | 1827 (10) | 732 (10) | 588 (10) | 300 (10) | 207 (11) |
| Not received, unknown reason | 4082 (23) | 1795 (25) | 1288 (21) | 637 (20) | 362 (19) |
Statistically significant at p < 0.001.
Unadjusted and adjusted logistic and multinomial regression models examining associations of BMI category with treatments received are given in Table 3. A table with estimates for covariates is available in Table S1. BMI was associated with receipt of any surgery among patients with a BMI 35.0+ kg/m2 (OR = 0.74, 95% CI: 0.55, 0.99) in unadjusted models; however, this association was not statistically significant after adjustment for age, subtype, stage, breast cancer treatment (chemotherapy, hormone therapy, radiation therapy), insurance, race, and median income (0.74 (0.53, 1.04)). In both unadjusted and adjusted models, patients with higher BMI who had surgery had lower odds of reconstruction relative to the referent group (i.e., those with BMI 18.5–24.9 kg/m2 who received lumpectomy); this inverse relationship appeared dose dependent, with increasingly lower odds in each increasing category of BMI (25.0–29.9 kg/m2 aOR = 0.81, 95% CI: 0.71, 0.93; 30.0–34.9 kg/m2 aOR = 0.62, 95% CI: 0.51, 0.74; 35.0+ kg/m2 aOR = 0.44, 95% CI: 0.34, 0.57). We also conducted a sensitivity analysis for the reconstruction model excluding patients who received a lumpectomy, which yielded similar findings (Table S2). BMI was inversely associated with receiving chemotherapy among patients with a BMI of 25.0–29.9 kg/m2 (OR = 0.85, 95% CI: 0.79, 0.91) or 30.0–34.9 kg/m2 (OR = 0.91, 95% CI: 0.83, 0.99) in unadjusted models, but not multivariable adjusted models. Further, in both unadjusted and adjusted models, patients with higher BMI were between 14% and 22% more likely to receive hormone therapy (25.0–29.9 kg/m2 aOR = 1.14, 95% CI: 1.03, 1.26; 30.0–34.9 kg/m2 aOR = 1.15, 95% CI: 1.01, 1.30; 35.0+ kg/m2 aOR = 1.22, 95% CI: 1.04, 1.42). In unadjusted models, BMI was associated with receipt of chemotherapy among patients with a BMI of 25.0–29.9 kg/m2 (0.85 (0.79, 0.91)) and 30.0–34.9 kg/m2 (0.91 (0.83, 0.99)); after multivariable adjustment, we only observed a significant association among those with a BMI of 30.0–34.9 kg/m2 (aOR = 1.21, 95% CI: 1.07, 1.36). Results were quantitatively similar in a sensitivity analysis restricting all models to only HR+/HER2− patients (data not shown).
TABLE 3.
Logistic regression and multinomial models for odds of receiving certain treatments among breast cancer cases diagnosed 2010–2020, in the Iowa Cancer Registry.
| BMI 25.0–29.9 kg/m2 (REF = 18.5–24.9) | BMI 30.0–34.9 kg/m2 (REF = 18.5–24.9) | BMI 35.0+ kg/m2 (REF = 18.5–24.9) | ||||
|---|---|---|---|---|---|---|
| Unadjusted model | Adjusted model | Unadjusted model | Adjusted model | Unadjusted model | Adjusted model | |
| OR (CI) | OR (CI) | OR (CI) | OR (CI) | OR (CI) | OR (CI) | |
| Logistic regression models a | ||||||
| Any surgery | 1.02 (0.82, 1.28) | 0.97 (0.75, 1.25) | 1.00 (0.76, 1.30) | 0.92 (0.68, 1.24) | 0.74 (0.55, 0.99) | 0.74 (0.53, 1.04) |
| Reconstruction b | 0.61 (0.54, 0.69) | 0.81 (0.71, 0.93) | 0.45 (0.38, 0.53) | 0.62 (0.51, 0.74) | 0.36 (0.28, 0.44) | 0.44 (0.34, 0.57) |
| Chemotherapy | 0.85 (0.79, 0.91) | 1.08 (0.97, 1.19) | 0.91 (0.83, 0.99) | 1.21 (1.07, 1.36) | 0.90 (0.81, 1.00) | 1.07 (0.92, 1.24) |
| Hormone therapy c | 1.16 (1.06, 1.27) | 1.14 (1.03, 1.26) | 1.21 (1.08, 1.36) | 1.15 (1.01, 1.30) | 1.29 (1.13, 1.49) | 1.22 (1.04, 1.42) |
| Radiation therapy | 1.22 (1.13, 1.31) | 1.07 (0.96, 1.18) | 1.29 (1.18, 1.41) | 1.12 (0.98, 1.27) | 1.26 (1.13, 1.40) | 0.90 (0.77, 1.05) |
| Multinomial model: extent of surgery (REF = lumpectomy) d | ||||||
| Unilateral mastectomy | 0.73 (0.67, 0.79) | 0.74 (0.68, 0.81) | 0.73 (0.66, 0.81) | 0.75 (0.67, 0.83) | 0.61 (0.53, 0.69) | 0.61 (0.53, 0.70) |
| Bilateral mastectomy | 0.67 (0.60, 0.74) | 0.80 (0.71, 0.90) | 0.64 (0.56, 0.73) | 0.79 (0.69, 0.91) | 0.68 (0.58, 0.79) | 0.81 (0.69, 0.96) |
Note: Bold font indicates statistical significance at p < 0.05.
Covariates included in adjusted models are age, subtype, stage, breast cancer treatment (extent of surgery, chemotherapy, radiation, hormone therapy), insurance, race, and median income.
Reconstruction is among those who received surgery.
Hormone therapy models were restricted to HR+ patients.
Covariates included in adjusted models are age, subtype, stage, treatment facility's CoC accreditation status, insurance, race, and rurality.
Finally, we examined associations of BMI with extent of surgery (i.e., receipt of unilateral or bilateral mastectomy, relative to lumpectomy). In the multinomial model adjusted for age, subtype, stage, breast cancer treatment, insurance, race, and median income, patients in higher BMI categories were less likely to receive unilateral mastectomy and bilateral mastectomy compared to lumpectomy, with odds of receiving these treatments appearing to decrease with increasing BMI (Table 3). Compared to patients with a BMI 18.5–24.9 kg/m2, those with a BMI 25.0–29.9 kg/m2 were 26% less likely to receive unilateral mastectomy (aOR = 0.74, 95% CI: 0.68, 0.81) and 20% less likely to receive bilateral mastectomy (aOR = 0.80, 95% CI: 0.71, 0.90). Those with a BMI 30.0–34.9 kg/m2 were 25% less likely to receive unilateral mastectomy (aOR = 0.75, 95% CI: 0.67, 0.83) and 21% less likely to receive bilateral mastectomy (aOR = 0.79, 95% CI: 0.69, 0.91). Those with a BMI of 35.0 kg/m2 or greater were 39% less likely to receive unilateral mastectomy (aOR = 0.61, 95% CI: 0.53, 0.70) and 19% less likely to receive bilateral mastectomy (aOR = 0.81, 95% CI: 0.69, 0.96). A table with estimates for covariates is available in Table S3.
4. Discussion
In this study, we assessed associations of BMI with treatments received among a population‐based sample of Iowa breast cancer patients diagnosed 2010–2020. While there was no difference by BMI in whether or not a patient received surgery, breast cancer patients with a higher BMI were more likely to receive lumpectomy and less likely to receive unilateral mastectomy, bilateral mastectomy, and reconstruction, with odds of receiving these treatments decreasing as BMI increased. In contrast, patients with higher BMI were more likely to receive hormone therapy than patients with lower BMI. These findings suggest breast cancer patients in larger bodies receive different treatment than those in smaller/straight‐sized bodies. Future research is warranted to understand reasons behind these differences in treatments received, both to ensure breast cancer patients with higher BMIs are receiving adequate and appropriate cancer care and to understand whether these differences in treatment contribute to observed differences in survival [5, 7, 8, 9, 10].
Among patients who received surgery, those in our study sample with higher BMI were more likely to receive lumpectomy than unilateral mastectomy or bilateral mastectomy compared to patients with lower BMI. This difference could be due to a perceived increased risk of surgical and post‐operative complications among those in larger bodies. Patients with higher BMI may experience complications during surgery that could influence a provider's decision to recommend more extensive surgery, such as increased difficulties with anesthesia, intubation, longer operative time, and increased post‐surgical complications such as a higher risk for infection and poor wound healing [11, 33, 34, 35, 36]. Patients with higher BMI tend to have larger breasts and so are more likely to be able to undergo lumpectomy with a good cosmetic result, even with larger tumors [11]. Since bilateral mastectomy does not improve survival in average‐risk women [37], providers may be reticent to offer this most‐extensive surgical treatment to their patients with higher BMI, for the reasons stated above.
Patients with higher weight may also be more likely to have concurrent comorbidities that could affect their treatment, such as diabetes and cardiovascular disease [38]. Unfortunately, there is a lack of information specific to comorbidity prevalence among individuals with both clinical obesity and breast cancer, although a small number of studies indicate these patients were more likely to have a history of hypertension and diabetes [20, 39]. Given our study design, we were unable to ascertain whether differences in treatments received by BMI were due to provider concerns, patient choice, or a combination thereof. Additionally, we were unable to identify specific patient risk factors for contralateral breast cancer, such as rates of deleterious genetic mutations or strong family history that would make bilateral mastectomy appropriate. Additional research is warranted to elucidate how shared decision making is occurring between cancer treatment providers and patients with higher BMI, and/or whether shared decision making varies by BMI in such a way that drives observed differences.
A lower likelihood of being offered reconstruction among patients with higher BMI may also explain higher receipt of lumpectomy over mastectomy among this group [35, 36]. There is some evidence to suggest patients with higher BMI have increased risk for complications after reconstruction, including necrosis, deep vein thrombosis and embolisms, and unplanned reoperation [33, 34, 40, 41, 42, 43], which could dissuade providers from offering reconstruction for patients in larger bodies. Perceived satisfaction with surgery may also contribute; although, there is mixed evidence regarding whether patients with higher BMI have lower quality of life and satisfaction post‐reconstruction than those with lower BMI [44, 45, 46]. Some studies assessing post‐reconstruction satisfaction up to 3 years after surgery suggest that patients with higher BMI have decreased esthetic satisfaction compared to those with lower BMI [41, 42]. However, others show no difference in esthetic or general satisfaction scores for certain types of reconstruction post‐surgery [40, 45, 46]. Patient factors, cost, surgeon expertise, and institutional resources may also impact the decision to receive breast reconstruction post‐mastectomy [47] While we were unable to assess these latter factors in our study, future research may consider exploring if and how weight impacts one's decision to offer (if a provider) or receive (if a patient) breast reconstruction post‐mastectomy, and its interrelation with other factors known to impact receipt.
In addition to differences in surgery types received, we observed that patients with a higher BMI were more likely to receive hormone therapy, and in some cases, chemotherapy, compared to those with lower BMI. Given that patients with higher BMI were more likely to receive lumpectomy and less likely to receive mastectomy, this may in turn impact the likelihood of receiving radiation therapy, although we did not observe differences in adjusted models. Alternatively, concerns of increased risk of recurrence among higher BMI patients [12] could prompt providers to provide more systemic therapy to those individuals. Previous studies have also indicated that higher BMI patients receive lower doses of chemotherapy due to concerns regarding toxicity [48, 49, 50], and/or a perceived pharmacokinetic difference for patients in larger bodies, which may impact treatment effectiveness [51]. Unfortunately, we were unable to assess this in our study, due to the nature of the available data (i.e., chemotherapy as a yes/no variable). In addition, type and timing of chemotherapy is strongly associated with breast cancer subtype, which in turn is associated with metabolic syndrome, one component of which is higher BMI [52]. Thus, it is possible that observed associations of BMI with chemotherapy may have been affected by breast cancer subtype in such a way that was not adequately addressed by our model adjustments. However, we do not anticipate that such residual confounding would necessarily impact receipt of chemotherapy as defined herein (i.e., yes/no). Further research is needed on differences in receipt of chemotherapy by body size, and its impact on outcomes for those in larger bodies; in particular, given the lack of specific chemotherapy agent and dosing in the registry, and detailed tumor biomarkers, further research which includes these considerations is warranted.
While some treatment decisions are likely based on a patient's health and likelihood for complications, we cannot rule out the possibility that anti‐fat bias (i.e., weight stigma) impacts how a provider approaches a patient's treatment [53]. While we were unable to assess weight stigma in our study, it could contribute to observed differences in received treatments between BMI groups. Little research has assessed the impact of provider anti‐fat bias on cancer treatment and outcomes, in part because no studies quantitatively assess provider weight bias or patient experiences of weight stigma during cancer treatment [54]. A limited body of research has examined qualitative reports of weight stigma in cancer treatment and reported stigmatizing experiences during cancer treatment including being offered less‐invasive treatment options (e.g., unilateral vs. bilateral mastectomy), mistreatment, and lack of available equipment to accommodate larger body sizes [15, 55, 56]. Weight stigma is known to affect healthcare for people in larger bodies: a majority of individuals with obesity report experiencing weight‐based stigma from medical providers [57], which impacts quality and outcomes of care [58]. In the case of cancer treatment, weight‐based stigma may influence what treatment options are presented to patients, with different (or fewer) treatment options offered to those in larger bodies. Due to limited knowledge on how provider decision‐making is impacted by a patient's weight throughout the cancer continuum, future research should quantitatively assess patient experiences of weight stigma and provider decision‐making during breast cancer treatment to determine whether weight‐based bias impacts breast cancer treatment and subsequent outcomes.
There are strengths and limitations of this work that should be considered when interpreting results. The main strength of this study is linkage of cancer registry data with driver's license data to obtain weight information, which is novel. The data source also allows for studying a large population‐based data sample, which increases generalizability of our findings. This topic area is understudied; therefore, this study contributes to the limited body of knowledge of the relationship between obesity and breast cancer treatment. However, this study is not without limitations. SEER data does not collect information on comorbidities, which limits our understanding of how other conditions impacted treatment decisions. Further, while we adjust for stage, receptor status, and grade in our models, there may remain residual confounding without adjustment for additional tumor‐specific information (e.g., Oncotype Dx). There has also been concern regarding the sensitivity of chemotherapy and radiation data in SEER [59], as noted in the methods. This could increase risk for misclassification of treatment status in this study (i.e., underestimate receipt of chemotherapy), but is unlikely to be differential based on demographic characteristics. Additionally, weight on driver's licenses is self‐reported and may not accurately represent whether a patient has obesity. We restricted our sample based on individuals that had a driver's license issue date within the 8 years prior to diagnosis; however, weight may change over time, and we cannot know if the issuance date on the license matches the date of height/weight self‐report. Nevertheless, positive predictive value is likely to be high, meaning that all patients classified as having obesity in this study likely do [60]. While some of those not classified as having obesity in this study may, in reality, have a BMI over 30 kg/m2, the resulting misclassification would likely bias our results toward the null and is unlikely to be differential based on demographic characteristics. Additionally, while we adjust for breast cancer subtype in each model, we note that given biologic and treatment differences between subtypes, it would have been ideal to stratify analyses accordingly. Unfortunately, given smaller cell sizes in some of the higher BMI categories, particularly in the multi‐variable adjusted analyses, we were unable to conduct stratified analyses with confidence. Finally, BMI is not an accurate measure of health and is subject to bias by several factors [61, 62]; however, despite issues with this measure, it is still used for clinical decision making and allows for comparability of our results with other studies.
5. Conclusions
This study assessed differences in breast cancer treatments received by BMI, and results suggest patients with higher BMI were more likely to receive less extensive surgery (i.e., lumpectomy, no reconstruction, more likely to receive hormone therapy), controlling for tumor characteristics. Future research is warranted to explore whether the differences observed herein translate into differences in guideline concordance of breast cancer treatment, as well as drivers of BMI‐based differences in breast cancer treatment and impacts on cancer outcomes, including weight‐based disparities.
Author Contributions
All authors contributed to the study conception and design. Data analysis was conducted by Amanda Kahl and Breanna Blaess, with oversight by Sarah Nash. The first draft of the manuscript was written by Breanna Blaess and Sarah Nash, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Funding
This project was supported by an Early Career Scholar Award from the University of Iowa Office of the Vice President for Research to Sarah Nash. It was also supported by the National Institutes of Health (P30 CA086862).
Ethics Statement
This study was given expedited ethics approval by the University of Iowa Institutional Review Board (#202204028).
Consent
A waiver of consent was received from the University of Iowa Institutional Review Board.
Conflicts of Interest
The authors declare no conflicts of interest.
Supporting information
Table S1: Odds of receiving certain treatments among breast cancer cases diagnosed 2010–2020, in the Iowa Cancer Registry, with covariate estimates provided.
Table S2: Sensitivity analysis comparing reconstruction models: (1) including lumpectomy patients, (2) excluding lumpectomy patients, and (3) excluding lumpectomy patients and adjusting for extent of surgery.
Table S3: Multinomial models among patients that received breast cancer surgery, cases diagnosed 2010–2020 within the Iowa Cancer Registry, with covariate estimates included. Reference category = Lumpectomy.
Acknowledgments
We would like to acknowledge our funding sources for this study: this project was supported by an Early Career Scholar Award from the University of Iowa Office of the Vice President for Research to Sarah Nash. It was also supported by the National Institutes of Health (P30 CA086862).
Data Availability Statement
The data that support the findings of this study are openly available in Surveillance, Epidemiology, and End Results Program at https://seer.cancer.gov/data/.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1: Odds of receiving certain treatments among breast cancer cases diagnosed 2010–2020, in the Iowa Cancer Registry, with covariate estimates provided.
Table S2: Sensitivity analysis comparing reconstruction models: (1) including lumpectomy patients, (2) excluding lumpectomy patients, and (3) excluding lumpectomy patients and adjusting for extent of surgery.
Table S3: Multinomial models among patients that received breast cancer surgery, cases diagnosed 2010–2020 within the Iowa Cancer Registry, with covariate estimates included. Reference category = Lumpectomy.
Data Availability Statement
The data that support the findings of this study are openly available in Surveillance, Epidemiology, and End Results Program at https://seer.cancer.gov/data/.