Examining Factors Associated with Experiencing Cardiac Arrhythmias in Black and White Breast Cancer Survivors Who Received Anthracyclines or Trastuzumab

doi:10.21203/rs.3.rs-5033513/v1

Purpose: Racial disparities exist regarding cardiovascular (CV) toxicities following breast cancer treatment; however, studies on racial differences in cardiac arrhythmias are lacking. This study examined associations between demographic and clinical factors and arrhythmia diagnosis in Black and White breast cancer survivors.

Methods: This study included a retrospective cohort of Black and White women who were diagnosed with breast cancer and who received potentially cardiotoxic treatment. Cardiac arrhythmia data were captured via International Classification of Diseases, Tenth and Ninth Versions (ICD-10 and ICD-9). Experiences with cardiac arrhythmias were compared across racial groups. The associations of demographic and clinical factors with cardiac arrhythmias were evaluated using logistic regression for all women and in race-stratified models.

Results: Cardiac arrhythmias were experienced by 33% of the total 860 women (mean (SD) age 50.3 [10.7] years). In bivariate analyses, Black women were more likely to experience arrhythmias when compared to White women (p=0.006). In race-stratified multivariable analysis, controlling for age and treatment, Black women >50 years were less likely to experience arrhythmias when compared to Black women <50 (adjusted odds ratio (OR): 0.50; 95% confidence interval [CI]: 0.29, 0.87) years. Black women with hypertension were 2.7 times more likely to experience arrhythmias than Black women without hypertension [95% CI: 1.52, 4.82]. White women with obesity were more likely to experience arrhythmias than White women with normal/underweight (OR: 1.97: [1.18, 3.28]).

Conclusion: Survivors with chronic conditions like hypertension and obesity may require enhanced cardiac surveillance. Further investigation into hypertension management in Black survivors may shed light on its impact on CV toxicities in this group.

Breast Cancer

Racial Disparities

Cardiac Arrhythmias

Hypertension

Cardiac arrhythmias, inclusive of atrial fibrillation and conduction disorders are of growing concern for women who receive potentially cardio-toxic therapy (e.g., anthracycline chemotherapies, human epidermal receptor 2 (HER2) targeted therapy) for breast cancer [1–3]. Concerns are valid as studies show that women with breast cancer are more likely to experience cardiovascular disease when compared to women without breast cancer, and older women with breast cancer are more likely to succumb to cardiovascular disease than to their breast cancer [4–7].

Cardiac arrhythmias, inclusive of diagnoses such as atrial fibrillation and conduction disorders, are one example of CV toxicities that remain understudied in women with breast cancer. While women with arrhythmias may experience symptoms, such as palpitations or dizziness, others may experience no symptoms as arrhythmias are sometimes coined as ‘silent’ [8]. More importantly, although the causative relationships are not fully understood, arrhythmias may lead to cardiomyopathy, heart failure, or even sudden cardiac death [9–11]. At present, few studies have examined the relationship between race and risk factors for cardiovascular disease and the development of arrhythmias upon receipt of potentially cardiotoxic treatment for breast cancer.

Although all women who receive cardiotoxic treatment are at-risk of CV toxicities, studies have reported on racial disparities in CV toxicities following breast cancer treatment. Black women are up to three times more likely to experience CV toxicities when compared to White women [12]. Reasons for this disparity are not clearly understood. Studies that examine racial differences in CV toxicities report that even after accounting for CV disease risk factors, such as hypertension and diabetes, and socioeconomic factors, the disparity persists [13, 14]. Most studies that examine racial differences in CV toxicities focus on heart failure and left ventricular dysfunction, highlighting a knowledge gap in potential disparities in cardiac arrhythmias.

The aims of this study were to examine racial differences for cardiac arrhythmias following a breast cancer diagnosis, assess the contribution of demographic and clinical factors, and comorbid conditions on an arrhythmia diagnosis, and to examine whether factors associated with arrhythmias differ by race. We hypothesized that Black women will be more likely to experience arrhythmias when compared to White women and that the contribution of clinical factors on experiences with arrhythmias will differ by race.

Study design and participants

Using electronic health data from Virginia Commonwealth University (VCU) Health System and the VCU Massey Comprehensive Cancer Center, we evaluated women diagnosed with American Joint Committee on Cancer (AJCC) stages I-III or unstaged invasive breast cancer who received an anthracycline-based chemotherapy and/or trastuzumab between 2009–2019. Women who self-identified as Black or White were included. We excluded women who had cardiovascular disease prior to breast cancer diagnosis. Our outcome of interest was cardiac arrhythmias. This study was approved by the VCU institutional review board.

To guide the abstraction of appropriate International Classification of Disease (ICD)-9 and 10 codes pertaining to arrhythmias, we consulted the International Cardio-Oncology Society consensus statement that defines CV toxicities including arrhythmias [15]. Diagnoses included, but are not limited to ventricular or atrial fibrillation, atrial flutter, tachycardia, and conduction disorders, including atrioventricular block.

Demographic factors assessed included race, age at diagnosis, marital status (married vs. unmarried), insurance (i.e., government-issued, private), and geography (metro vs. non metro). Clinical variables included AJCC stage, endocrine receptor, progesterone receptor, and human epidermal growth factor 2 status, and the type of cardiotoxic medication women received (i.e., anthracycline-based chemotherapy, trastuzumab, or both). Surgery type included mastectomy, lumpectomy, and re-excision of the biopsy site for gross or microscopic residual disease, classified as ‘other’. Additionally, comorbid conditions known to contribute to CV toxicities, such as hypertension and diabetes, were determined via ICD-9 or 10 codes while body mass index (BMI) at diagnosis was abstracted from the medical record.

Statistical analysis

Descriptive statistics, including means and frequencies, summarized for all variables for all women, across races, and for a cardiac arrhythmia diagnosis. Chi-square was used to assess associations with categorical variables and two-sample unpaired t-test under equal variance assumption were used to assess associations with continuous variables. Variables that were statistically significant at p < 0.05 in bivariate analysis were selected for inclusion in multivariable models. The following covariates were controlled for in all multivariable analyses given their plausible associations with cardiovascular toxicities: age, BMI, trastuzumab use, and anthracycline chemotherapy use. SAS 9.4 was used to analyze all data [16].

A total of 860 women were included in these analyses. Most of the women in this sample were White (62%), married (55%), received a mastectomy (80%), and received anthracycline-based chemotherapy (78%) (Table 1). Compared to White women, Black women were younger (48 years old vs. 52 years old, p=0.002) at diagnosis, were unmarried (66.3% vs. 31.6%, p=0.000), had obesity (60.7% vs. 30.5%, p=0.000), and had a higher prevalence of hypertension (26.1%, vs. 6.2%, p=0.000) and diabetes (13.5% vs. 3.65, p=0.000).

Most women in our sample did not experience arrhythmias during or following treatment (67%). Black women had a higher prevalence of arrhythmias than White women (39.3% vs. 29.8%, p=0.004). Compared to women who did not experience an arrhythmia, women who experienced an arrhythmia were more likely have obesity (51.2% vs. 37.3%, p<0.001) and stage III breast cancer (23.0% vs. 15.0%, p=0.01). Differences in age were not significantly different between women who did and did not experience arrhythmias (p=0.15).

In the multivariable model with all women accounting for age, BMI, trastuzumab, and anthracycline use, race was no longer significantly associated with experiencing arrhythmias (Odds ratio (OR): 0.98 [95% Confidence Interval (CI): 0.69, 1.38]) (Table 3). Controlling for the same variables as for the model with all women, race-stratified multivariable models, revealed different patterns of associations with arrhythmias between Black and White women. Age was significant among Black women only and, interestingly, Black women that were > 50 years old were less likely to experience arrhythmias compared to Black women < 50 years old (0.50 [0.29, 0.87]) (Table 3). Hypertension was only significant for Black women. Black women with hypertension were more than twice as likely to experience arrhythmias than Black women without hypertension (2.66 [1.49, 4.73]). BMI was only significant for White women. White women with obesity were more likely to experience arrhythmias than White women with normal/underweight (1.98 [1.20, 3.28]). There was not a significant association in experiencing arrhythmias between White women with overweight and those with normal/underweight.

This is one of the first studies that characterize racial differences in factors associated with cardiac arrhythmias in breast cancer survivors. Although odds of experiencing arrhythmias were higher amongst Black women relative to White women in bivariate analysis, after controlling for covariates (e.g., age, BMI, treatment), this association was no longer significant. In addition, this study highlights the importance of clinical targets, specifically chronic conditions that are risk factors for CV toxicity, that may improve outcomes in women. Our results suggest that chronic comorbid conditions, namely hypertension, diabetes, obesity not only contribute to arrhythmias, but they may also play a role in interracial differences in experiences with cardiac arrhythmias. Hypertension was significantly associated with cardiac arrhythmias amongst Black women only while the same was true regarding obesity amongst White women only. This finding, to our knowledge, has not been previously reported.

Approximately 33% of women experienced cardiac arrhythmias following a breast cancer diagnosis in this study. Proper management of cardiac arrhythmias during and following treatment for breast cancer is critical during survivorship, particularly as studies show that arrhythmias may lead to additional cardiac complications, such as ischemic stroke, tachycardia-induced cardiomyopathy, and heart failure [17–20]. A recent study that utilized the Surveillance, Epidemiology, and End-Results-Medicare-Linked database to investigate atrial fibrillation in women with breast cancer reported an association between increased 1-year cardiovascular mortality in women with an atrial fibrillation diagnosis following a breast cancer diagnosis [20]. In addition to the need for enhanced surveillance, future research is needed to assess the onset of additional CV toxicities and CV-related mortality associated with arrhythmias following a breast cancer diagnosis.

In our study, we found that after controlling for covariates of interest, there was no differential association in the development of arrhythmias when comparing Black and White women. Though not specifically focused on arrhythmias, in studies of women with breast cancer, most find that Black women are more likely to experience CV toxicities than White women, even after controlling for plausible factors related to CV toxicities (e.g., cardiotoxic treatment, hypertension) [13, 21]. Conversely, in other studies, after accounting for the aforementioned factors, racial differences were no longer significant [22]. Additionally, mixed findings amongst women with cancer prompt a need to understand the roles of treatment modalities (i.e., anthracycline-based chemotherapies, trastuzumab, radiation) and individual CV toxicities mechanisms on racial disparities in CV toxicities.

Race stratified analyses revealed that younger Black women were more likely to experience arrhythmias than older Black women. This is a novel finding as older age remains a risk factor for arrhythmias and other CV toxicities, in general. One possible explanation for this finding involves adherence to anti-hypertensive medications and subpar hypertension management. A study of Black women who were prescribed antihypertensive medications found that while women of all groups had poor adherence, the highest nonadherence was amongst younger Black women, between ages 40–49 [23]. Future work is needed that centers young Black breast cancer survivors and seeks to understand multilevel contributors (e.g., stress, cancer, and hypertension care delivery) that may contribute to their risk of cardiac arrhythmias. This is especially salient as a recent study by Tanake et al. reported an increase in cardiovascular deaths related to atrial fibrillation among younger adults [24].

Comorbid conditions, namely those that are risk factors for CV toxicities, were drivers of arrhythmias in Black and White women. Patterns, however, varied by race. Amongst Black women only, hypertension was significantly associated with arrhythmias. As mentioned for younger Black women, this may be due in part to nonadherence to antihypertensive medication and inadequate hypertension control. A study by Hershman et al. reported that Black breast cancer survivors were more likely to be nonadherent when compared to breast cancer survivors of other races and ethnicities. Additionally, nonadherence was associated with a greater risk of cardiac events following a breast cancer diagnosis [25]. It is also salient to consider guidelines for treating hypertension in Black women. The most recent clinical practice guidelines recommend two or more anti-hypertensive medications to achieve a blood pressure of < 130/80 mm HG, “especially in African American adults [26].” Obesity, a known risk factor for CV toxicities, was only significant for White women. These findings not only highlight a need for increased cardiac surveillance in women with comorbid conditions but, with regard to BMI and obesity, there may be better measures, such as waist circumference or visceral fat measurements, that may provide more accurate risk predictions for arrhythmias and other CV toxicities.

We acknowledge that this study has limitations, such as its retrospective design. We were unable to include smoking and radiation, known risk factors of CV toxicities, in the analyses, as these data were not available. In addition, the sample for this study was from one healthcare system, limiting generalizability to other patient populations. Despite the limitations, there are noted strengths to report. This study included a high representation of Black breast cancer survivors, when compared to similar studies, allowing for race-stratified analysis. While some risk factors were excluded, this study did include BMI, a factor that has not been fully explored with regard to racial differences in CV toxicities. This study also included more age and payer-type diversity, unlike the other studies that mostly report on women administrative databases who are 66 years of age and older who have Medicare only.

Compared to older Black women, younger Black women were more likely to experience arrhythmias. Additionally, the differential impact of comorbid conditions (i.e., obesity, hypertension) on experiences with cardiac arrhythmias supports further research on behavioral factors and biological mechanisms that may inform enhanced surveillance and cardiac management for Black and White breast cancer survivors who receive cardiotoxic treatments. These approaches may ultimately reduce racial disparities in breast cancer morbidity and mortality.

Compliance with Ethical Standards

Conflict of Interest: The authors declare that they have no conflict of interest.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Institutional Review Board at Virginia Commonwealth University.

Author Contribution

A.L.S. contributed to the study conception and wrote the main manuscript text. J.Z and J.H contributed to data analysis and prepared the tables. All authors provided revisions. All authors reviewed the manuscript.

Acknowledgement

Acknowledgments: This study was funded by the National Institutes of Health/National Cancer Institute K99CA250638 (Sutton). Services and products in support of this research project were generated by the VCU Massey Cancer Center Cancer Informatics Shared Resource, supported, in part, with funding from NIH-NCI Cancer Center Support Grant P30CA016059.

Data Availability

Availability of data and material. Data archiving is not mandated but will be made available on reasonable request.

Schwartz RG, McKenzie WB, Alexander J, Sager P, D'Souza A, Manatunga A, Schwartz PE, Berger HJ, Setaro J, Surkin L et al (1987) Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography. Am J Med 82(6):1109–1118
Armenian SH, Lacchetti C, Barac A, Carver J, Constine LS, Denduluri N, Dent S, Douglas PS, Durand JB, Ewer M et al (2017) Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 35(8):893–911
Amir E, Seruga B, Niraula S, Carlsson L, Ocaña A (2011) Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst 103(17):1299–1309
Ramin C, Schaeffer ML, Zheng Z, Connor AE, Hoffman-Bolton J, Lau B, Visvanathan K (2021) All-Cause and Cardiovascular Disease Mortality Among Breast Cancer Survivors in CLUE II, a Long-Standing Community-Based Cohort. J Natl Cancer Inst 113(2):137–145
Patnaik JL, Byers T, DiGuiseppi C, Dabelea D, Denberg TD (2011) Cardiovascular disease competes with breast cancer as the leading cause of death for older females diagnosed with breast cancer: a retrospective cohort study. Breast Cancer Res 13(3):R64
Gernaat SAM, Boer JMA, van den Bongard DHJ, Maas A, van der Pol CC, Bijlsma RM, Grobbee DE, Verkooijen HM, Peeters PH (2018) The risk of cardiovascular disease following breast cancer by Framingham risk score. Breast Cancer Res Treat 170(1):119–127
Buttros DAB, Branco MT, Orsatti CL, Almeida-Filho BS, Nahas-Neto J, Nahas EAP (2019) High risk for cardiovascular disease in postmenopausal breast cancer survivors. Menopause 26(9):1024–1030
Dilaveris PE, Kennedy HL (2017) Silent atrial fibrillation: epidemiology, diagnosis, and clinical impact. Clin Cardiol 40(6):413–418
Middlekauff HR, Stevenson WG, Stevenson LW (1991) Prognostic significance of atrial fibrillation in advanced heart failure. A study of 390 patients. Circulation 84(1):40–48
Huizar JF, Ellenbogen KA, Tan AY, Kaszala K (2019) Arrhythmia-Induced Cardiomyopathy: JACC State-of-the-Art Review. J Am Coll Cardiol 73(18):2328–2344
Carson PE, Johnson GR, Dunkman WB, Fletcher RD, Farrell L, Cohn JN (1993) The influence of atrial fibrillation on prognosis in mild to moderate heart failure. The V-HeFT Studies. The V-HeFT VA Cooperative Studies Group. Circulation 87(6 Suppl):Vi102–110
Sutton AL, Felix AS, Wahl S, Franco RL, Leicht Z, Williams KP, Hundley WG, Sheppard VB (2022) Racial disparities in treatment-related cardiovascular toxicities amongst women with breast cancer: a scoping review. J Cancer Surviv
Litvak A, Batukbhai B, Russell SD, Tsai HL, Rosner GL, Jeter SC, Armstrong D, Emens LA, Fetting J, Wolff AC et al (2018) Racial disparities in the rate of cardiotoxicity of HER2-targeted therapies among women with early breast cancer. Cancer 124(9):1904–1911
Al-Sadawi M, Hussain Y, Copeland-Halperin RS, Tobin JN, Moskowitz CS, Dang CT, Liu JE, Steingart RM, Johnson MN, Yu AF (2021) Racial and Socioeconomic Disparities in Cardiotoxicity Among Women With HER2-Positive Breast Cancer. Am J Cardiol 147:116–121
Herrmann J, Lenihan D, Armenian S, Barac A, Blaes A, Cardinale D, Carver J, Dent S, Ky B, Lyon AR et al (2022) Defining cardiovascular toxicities of cancer therapies: an International Cardio-Oncology Society (IC-OS) consensus statement. Eur Heart J 43(4):280–299
R Core Team (2024) _R: A Language and Environment for Statistical Computing_. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/
Nerheim P, Birger-Botkin S, Piracha L, Olshansky B (2004) Heart failure and sudden death in patients with tachycardia-induced cardiomyopathy and recurrent tachycardia. Circulation 110(3):247–252
Kim DY, Kim SH, Ryu KH (2019) Tachycardia induced Cardiomyopathy. Korean Circ J 49(9):808–817
Anter E, Jessup M, Callans DJ (2009) Atrial fibrillation and heart failure: treatment considerations for a dual epidemic. Circulation 119(18):2516–2525
Halcox JPJ, Wareham K, Cardew A, Gilmore M, Barry JP, Phillips C, Gravenor MB (2017) Assessment of Remote Heart Rhythm Sampling Using the AliveCor Heart Monitor to Screen for Atrial Fibrillation: The REHEARSE-AF Study. Circulation 136(19):1784–1794
Doyle JJ, Neugut AI, Jacobson JS, Wang J, McBride R, Grann A, Grann VR, Hershman D (2007) Radiation therapy, cardiac risk factors, and cardiac toxicity in early-stage breast cancer patients. Int J Radiat Oncol Biol Phys 68(1):82–93
Tsai HT, Isaacs C, Fu AZ, Warren JL, Freedman AN, Barac A, Huang CY, Potosky AL (2014) Risk of cardiovascular adverse events from trastuzumab (Herceptin(®)) in elderly persons with breast cancer: a population-based study. Breast Cancer Res Treat 144(1):163–170
Abel WM, Efird JT (2013) The Association between Trust in Health Care Providers and Medication Adherence among Black Women with Hypertension. Front Public Health 1:66
Tanaka Y, Shah NS, Passman R, Greenland P, Lloyd-Jones DM, Khan SS (2021) Trends in Cardiovascular Mortality Related to Atrial Fibrillation in the United States, 2011 to 2018. J Am Heart Assoc 10(15):e020163
Hershman DL, Accordino MK, Shen S, Buono D, Crew KD, Kalinsky K, Trivedi MS, Hur C, Hu J, Unger JM et al (2020) Association between nonadherence to cardiovascular risk factor medications after breast cancer diagnosis and incidence of cardiac events. Cancer 126(7):1541–1549
Whelton PK, Carey RM, Aronow WS, Casey DE Jr., Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW et al (2017) ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2018, 71(6):e13-e115

Table 1. Demographic and Clinical Characteristics of Black and White Breast Cancer Survivors

Participant Characteristics

Total

N = 860

Black

(N=326, 37.9%)

White

(N=534, 62.1%)

p-value

Age, y (mean ± SD)

50.3 ±10.7

48.4 ±11.0

51.5 ± 10.4

0†

Age, n (%)

< 50

> 50

439 (51.0)

421 (49.0)

188 (57.7)

138 (42.3)

251 (47.0)

283 (53.0)

0.002

Marital Status, n (%)

Married

Unmarried

475 (55.2)

385 (44.8)

110 (33.7)

216 (66.3)

365 (68.4)

169 (31.6)

0

Insurance Status, n (%)

Government-Issued

Private

Uninsured

Self-pay

Missing

163 (19.0)

512 (59.5)

97 (11.3)

84 (9.8)

4 (0.5)

72 (22.1)

158 (48.5)

51 (15.6)

41 (12.6)

4 (1.2)

91 (17.0)

354 (66.3)

46 (8.6)

43 (8.1)

0

Geography, n (%)

Metro

Non-metro

Missing

737 (85.7)

120 (14.0)

3 (0.3)

273 (83.7)

51 (15.6)

2 (0.6)

464 (87.0)

69 (12.9)

1 (0.2)

0.25

BMI, n (%)

Underweight

/Normal Weight

Overweight

Obesity

229 (26.6)

270 (31.4)

361 (42.0)

36 (11.0)

92 (28.2)

198 (60.7)

193 (36.1)

178 (33.3)

163 (30.5)

0

Stage, n (%)

I

II

III

NA

176 (20.5)

362 (42.1)

152 (17.7)

170 (19.8)

59 (18.1)

142 (43.6)

66 (20.2)

59 (18.1)

117 (21.9)

220 (41.2)

86 (16.1)

111 (20.8)

0.18

ER Status, n (%)

Negative

Positive

Unknown

377 (43.8)

468 (54.4)

15 (1.7)

184 (56.4)

136 (41.7)

6 (1.8)

193 (36.1)

332 (62.2)

9 (1.7)

0

PR Status, n (%)

Negative

Positive

Unknown

461 (53.6)

386 (44.9)

13 (1.5)

216 (66.3)

107 (32.8)

3 (0.9)

245 (45.9)

279 (52.2)

10 (1.9)

0

HER2 Status, n (%)

Negative

Positive

Unknown

286 (33.3)

204 (23.7)

370 (43.0)

140 (42.9)

78 (23.9)

108 (33.1)

146 (27.3)

126 (23.6)

262(49.1)

0.02

Surgery Type, n (%)

Lumpectomy or Excisional Biopsy

Mastectomy

Other

Missing

103 (12.0)

691 (80.3)

34 (4.0)

32 (3.7)

25 (7.7)

273 (83.7)

9 (2.8)

19 (5.8)

78 (14.6)

418 (78.3)

25 (4.7)

13 (2.4)

0.005

Anthracycline-based Chemotherapy, n (%)

No

Yes

190 (22.1)

670 (77.9)

64 (19.6)

262 (80.4)

126 (23.6)

408 (76.4)

0.17

Trastuzumab, n (%)

No

Yes

561 (65.2)

299 (34.8)

225 (69.0)

101 (31.0)

336 (62.9)

198 (37.1)

0.07

Diabetes, n (%)

No

Yes

797 (92.7)

63 (7.3)

282 (86.5)

44 (13.5)

515 (96.4)

19 (3.6)

0

Hypertension, n (%)

No

Yes

742 (86.2)

118 (13.8)

241 (73.9)

85 (26.1)

501 (93.8)

33 (6.2)

0

Arrhythmias, n (%)

No

Yes

573 (66.6)

287 (33.4)

198 (60.7)

128 (39.3)

375 (70.2)

159 (29.8)

0.004

†P-value from the two-sample unpaired t-test under the equal variance assumption

Table 2. Demographic and Clinical Factors of Black and White Breast Cancer Survivors by Arrhythmia Diagnosis Status

Participant Characteristics

Experienced Arrhythmias

No (N=573, 66.6%)

Yes (N=287, 33.4%)

p-value

Age, y (mean ± SD)

50.7 ±10.5

49.8 ± 11.1

0.15†

Age, n (%)

< 50

> 50

285 (49.7)

288 (50.3)

154 (53.7)

133 (46.3)

0.28

Race, n (%)

Black

White

198 (34.6)

375 (65.4)

128 (44.6)

159 (55.4)

0.004

Marital Status, n (%)

Married

Unmarried

329 (57.4)

244 (42.6)

146 (50.9)

141 (49.1)

0.07

Insurance Status, n (%)

Government-Issued

Private

Uninsured

Self-pay

Missing

103 (18.0)

355 (62.0)

62 (10.8)

51 (8.9)

2 (0.3)

60 (20.9)

157 (54.7)

35 (12.2)

33 (11.5)

2 (0.7)

0.24

Geography, n (%)

Metro

Non-metro

Missing

494 (86.2)

76 (13.3)

3 (0.5)

243 (84.7)

44 (15.3)

0 (0.0)

0.43

BMI, n (%)

Underweight/Normal Weight

Overweight

Obesity

166 (29.0)

193 (33.7)

214 (37.3)

63 (22.0)

77 (26.8)

147 (51.2)

<0.001

Stage, n (%)

I

II

III

NA

127 (22.2)

241 (42.1)

86 (15.0)

119 (20.8)

49 (17.1)

121 (42.2)

66 (23.0)

51 (17.8)

0.01

ER Status, n (%)

Negative

Positive

Unknown

248 (44.3)

316 (55.1)

9 (1.6)

129 (44.9)

152 (53.0)

6 (2.1)

0.59

PR Status, n (%)

Negative

Positive

Unknown

305 (53.2)

260 (45.4)

8 (1.4)

156 (54.4)

126 (43.9)

5 (1.7)

0.64

HER2 Status, n (%)

Negative

Positive

Unknown

178 (31.1)

133 (23.2)

262 (45.7)

108 (37.6)

71 (24.7)

108 (37.6)

0.50

Surgery Type, n (%)

Lumpectomy or Excisional Biopsy

Mastectomy

Other

Missing

81 (14.1)

450 (78.5)

27 (4.7)

15 (2.6)

22 (7.7)

241 (84.0)

7 (2.4)

17 (5.9)

0.008

Anthracycline-based Chemotherapy, n (%)

No

Yes

128 (22.3)

445 (77.7)

62 (21.6)

225 (78.4)

0.81

Trastuzumab, n (%)

No

Yes

379 (66.1)

194 (33.9)

182 (63.4)

105 (36.6)

0.43

Diabetes, n (%)

No

Yes

540 (94.2)

33 (5.8)

257 (89.5)

30 (10.5)

0.01

Hypertension, n (%)

No

Yes

518 (90.4)

55 (9.6)

224 (78.0)

63 (22.0)

0

†P-value from the two-sample unpaired t-test under the equal variance assumption

Table 3. Adjusted Odds Ratios of Experience with Cardiac Arrhythmias in All Women and by Race

Characteristics

All Women (n = 850)

OR (95% CI)

Black Women (n = 320)

OR (95% CI)

White Women (n = 530)

OR (95% CI)

Race

Black

White

1.02 (0.72, 1.43)

Reference

-

Age

> 50

< 50

0.77 (0.56, 1.06)

Reference

0.49 (0.28, 0.86)*

Reference

1.03 (0.69, 1.54)

Reference

Stage

II

III

Unknown

I

1.16 (0.75, 1.81)

1.83 (1.09, 3.07)*

0.93 (0.55, 1.59)

Reference

1.99 (0.95, 4.33)

3.24 (1.39, 7.84)**

2.25 (0.92, 5.60)

Reference

0.81 (0.47, 1.43)

1.29 (0.66, 2.52)

0.49 (0.24, 0.97)*

Reference

Trastuzumab

Yes

No

1.60 (1.03, 2.49)*

Reference

1.77 (0.83, 3.73)

Reference

1.41 (0.79, 2.47)

Reference

Anthracycline-based Chemotherapy

Yes

No

1.37 (0.80, 2.35)

Reference

0.76 (0.30, 1.89)

Reference

1.87 (0.93, 3.79)

Reference

Surgery Type

Lumpectomy or excisional biopsy

Other

Mastectomy

0.56 (0.33, 0.92)*

0.63(0.25, 1.42)

Reference

0.73 (0.27, 1.83)

2.04(0.46, 8.55)

Reference

0.44 (0.22, 0.84)*

0.32 (0.07, 0.96)

Reference

BMI

Obesity

Overweight

Normal/Underweight

1.54 (1.02, 2.33)*

1.03 (0.68, 1.58)

Reference

0.88 (0.38, 2.05)

0.59 (0.24, 1.47)

Reference

1.93 (1.17, 3.20)*

1.10 (0.67, 1.82)

Reference

Diabetes

Yes

No

1.43 (0.79, 2.55)

Reference

1.54 (0.72, 3.26)

Reference

2.02 (0.71, 5.79)

Reference

Hypertension

Yes

No

2.30 (1.47, 3.58)***

Reference

2.68 (1.51, 4.81)***

Reference

1.89 (0.86, 4.14)

Reference

*p<0.05

**p<0.01

***p<0.001

No competing interests reported.

Examining Factors Associated with Experiencing Cardiac Arrhythmias in Black and White Breast Cancer Survivors Who Received Anthracyclines or Trastuzumab

Status:

Version 1

Abstract

Introduction

Methods

Study design and participants

Statistical analysis

Results

Discussion

Declarations

Author Contribution

Acknowledgement

Data Availability

References

Tables

Additional Declarations

Status:

Version 1