Factors associated with longer endocrine therapy use by South Carolina Medicaid-insured breast cancer survivors

Abstract

Purpose

The objective of this study is to determine demographic, clinical, and pharmaceutical factors that are associated with longer endocrine therapy usage duration.

Methods

South Carolina Central Cancer Registry incidence data linked with South Carolina Medicaid prescription claims and administrative data were used. The study included a sample (N = 1399) of female South Carolina Medicaid recipients with hormone receptor-positive breast cancer diagnosed between 2000 and 2012 who filled at least one ET prescription. A series of multiple regression models were built to explore the association of demographic, clinical, and pharmaceutical factors with the endocrine therapy usage duration.

Results

Multiple linear regression analysis showed that none of the demographic or clinical factors tested were significantly associated with the endocrine therapy usage duration. However, the type of endocrine therapy taken as well as receipt of the prescriptions that could have been used to alleviate side-effects (adrenals, nonsteroidal anti-inflammatory agents, anti-inflammatory agents, and vitamins) were significantly associated.

Conclusion

Our study highlights the potential value of concurrent prescriptions for improving the endocrine therapy usage duration, with an optimal intervention point before 14 months post ET initiation. This work informs further research needed to test pharmacologic interventions that may significantly increase the endocrine therapy duration as well as other nonpharmacologic strategies for side-effect management.

Keywords

Endocrine therapy Tamoxifen aromatase inhibitors breast cancer cancer surviorship

Introduction

Endocrine therapy (ET) has been used for decades as the primary means of increasing disease-free survival in women with hormone receptor-positive Stage 0-III breast cancer, yet discontinuation rates remain high.^1,2 The percentage of tamoxifen users who discontinued treatment has been estimated to range from 15% to 20% in the first year of therapy to 31–60% at the end of five years.³ The percentage of aromatase inhibitor users who discontinued treatment ranged from 5% to 25% during the first two years of therapy.³ Studies examining both tamoxifen and aromatase inhibitor users showed discontinuation rates between 32% and 73% by the end of five years of treatment.³

Numerous studies have examined factors contributing toward nonadherent, nonpersistent ET use. The following subgroups have been highlighted as at-risk: low socioeconomic status,^4–6 low social support,^3,7,8 greater comorbidity,^7,8 greater drug cost,^3,7 greater side-effects,^3,8 lack of provider communication regarding the importance of ET,^3,8 extremes of age,^3,8 and follow-up care with a general practitioner versus a cancer specialist.^3,8

As literature has established, the Medicaid population is at high risk for poor ET usage,^4–6 with a lack of interventions targeted at this population.^9–12 Qualitative studies reveal that side-effects, primarily menopausal symptoms and/or joint pain, emerge as the major barrier to continuing ET for the recommended duration.^13–17 Tested interventions have focused on patient education and side-effect management.^9,18–21 Recent systematic reviews showed no meaningful improvements over usual care, highlighting the urgent need for more effective interventions.^9,21,22 Medications have been recommended to alleviate ET side-effects, including alpha-agonist hypertensives, antidepressants, anticonvulsants, adrenals, nonsteroidal anti-inflammatory agents, anti-inflammatory agents, and vitamins.^23–28 The most effective timing and methods for necessary intervention are still under development. The aim of this study is to identify demographic, clinical, and pharmaceutical factors that are associated with an individual's ET usage duration in hopes that these factors can better inform emerging interventions.

Methods

Data source

The study sample was identified using South Carolina Central Cancer Registry incidence data from 2000 to 2012 linked with South Carolina Medicaid prescription claims and administrative data from 2000 through 2016.²⁹ Probabilistic match by patient first name, last name, social security number, and date of birth was used for the linkage performed by the South Carolina Department of Revenue and Fiscal Affairs. Data were de-identified prior to release to the researchers. Clemson University and South Carolina Department of Health and Environmental Control Institutional Review Boards approved this study.

Sample

The sample included all women in the SC Cancer Registry who met the study inclusion criteria (N = 1399). Sample inclusion criteria were female South Carolina Medicaid recipients ages 18–64 at diagnosis with stage 0–III or unstaged hormone receptor-positive breast cancer diagnosed between 2000 and 2012 and who filled at least one ET prescription. Exclusion criteria were SEER summary stage 7 cancer, estrogen receptor-negative cancers, prior cancer diagnoses, cancer identification through autopsy or death certificate, and dual enrollment in Medicare (since Medicare prescription claim data were not available).

Dependent variable

ET included tamoxifen and the following aromatase inhibitors: Anastrozole/Arimidex, Letrozole/Femara, or Exemestane/Aromasin. Drugs were identified using therapeutic class and National Drug Codes from Medicaid prescription claims. ET usage duration was calculated as the number of months between the first and last ET prescription dispense dates using the date dispensed and days supplied variables from the South Carolina Medicaid pharmacy claims file. Participants were followed from the time of their first ET prescription filled through 2016. ET usage duration is important given that since 2014, the American Society of Clinical Oncology recommends ET usage to up to 10 years in some subgroups, following multiple trials demonstrating disease-free survival benefits for those who take ET for 5–10 years.^30–34

Independent variables

Independent variables included the factors hypothesized to be associated with ET usage duration based on literature review. The following demographic, clinical, and pharmaceutical factors were examined:

Demographic: race (white, African American, or other), age at diagnosis, marital status (married/unmarried), and rural/urban residency status (2013 Rural-Urban Continuum Codes).

Clinical: SEER summary breast cancer stage, receipt of chemotherapy (yes/no), and receipt of radiation therapy (yes/no).

Pharmaceutical: Type of endocrine therapy (Tamoxifen, Anastrozole/Arimidex, Exemestane/Aromasin, Letrozole/Femara, switched between aromatase inhibitors, switched between Tamoxifen and aromatase inhibitors), and filled alpha-agonist hypertensives prescription (yes/no), filled antidepressants prescription (yes/no), filled anticonvulsants prescription (yes/no), filled adrenals prescription (yes/no), filled nonsteroidal anti-inflammatory agents prescription (yes/no), filled anti-inflammatory agents prescription (yes/no), and filled vitamins prescription (B, C, D, K, and/or multivitamin) (yes/no). The prescriptions were identified by therapeutic class code and measured as ever having filled prescription during the study period as evidenced by Medicaid claims.

Provider specialty data had a high number of missing values and therefore was not included in the study.

Statistical analysis

Multiple linear regression models were built to explore the impact of demographic, clinical, and pharmaceutical factors on ET usage duration in months (α = 0.05). First, a series of models was made by singularly entering each of the independent variables with the dependent variable ET usage duration. Then, the combined effect of the independent variables that were significantly associated with the dependent variable was examined. Interactions terms were generated for each pair of significant independent variables and entered as a block to test for significant association with ET usage duration. The final model was generated by removing variables from the model that were no longer significant when controlling for other factors and adding the significant interaction terms. StataMP 14.0 was used for all analyses.

Results

The study sample consisted of 1399 hormone receptor-positive cancer survivors. Fifty-three percent of women in the study sample were white (N = 744), and 44% were African American (N = 622). The median age at diagnosis was 49 years (range: 21–64). Twenty-nine percent (N = 376) were single, 36% (N = 456) were married, and 16% (N = 210) were divorced. Following the 2013 Rural-Urban Continuum Codes for South Carolina, 79% (N = 1101) of the women resided in metropolitan counties. The breakdown by SEER summary breast cancer stage was as follows: Stage 0 (N = 164, 12%), Stage 1 (N = 576, 41%), Stage 2 (N = 24, 2%), Stage 3 (N = 530, 38%), Stage 4 (N = 88, 6%), and unknown (N = 17, 1%). Fifty-three percent (N = 743) of the sample had received chemotherapy, and 44% (N = 612) had received radiation therapy.

Forty-one percent (N = 577) of the women were taking Tamoxifen, and 36% were taking aromatase inhibitors (Anastrozole/Arimidex: N = 199, 14%, Exemestane/Aromasin: N = 34, 2%, Letrozole/Femara: N = 186, 13%, switched between different aromatase inhibitors: N = 91, 7%). Twenty-two percent (N = 312) of the women switched between Tamoxifen and aromatase inhibitors.

Eight percent (N = 110) had filled a prescription for alpha-agonist hypertensives, 60% (N = 838) had filled a prescription for antidepressants, 32% (N = 447) had filled a prescription for anticonvulsants, 60% (N = 843) had filled a prescription for adrenals, 57% (N = 801) had filled a prescription for nonsteroidal anti-inflammatory agents, 28% (N = 386) had filled a prescription for anti-inflammatory agents, and 27% (N = 379) had filled a prescription for vitamins (B, C, D, K, and/or multivitamins).

Multiple linear regression analysis showed that none of the demographic or clinical factors tested (race, age at diagnosis, marital status, and rural/urban status, SEER summary breast cancer stage, receipt of chemotherapy, receipt of radiation therapy) were significantly associated with ET usage duration. When base models were created with each of the pharmaceutical variables and ET usage duration as the dependent variable, each of the pharmaceutical variables were significantly associated with ET usage duration except alpha-agonist hypertensives (β = −1.80, p = 0.51). The results are shown in Table 1 as Models A–G.

Table 1.

Bivariate (Models A–G) and multiple regression (Model H) results for variables associated with endocrine therapy usage duration for the South Carolina Medicaid Population, 2000–2012.

	A	B	C	D	E	F	G	H
Constant	30.00 (1.07)**	33.37 (1.15)**	35.06 (0.88)**	31.23 (1.15)**	30.11 (1.09)**	34.09 (0.84)**	34.86 (0.85)**	17.22 (1.52)**
Type of endocrine therapy
Anastrozle/Arimidex	8.77 (2.11)**							9.22 (2.01)**
Exemestane/Aromasin	1.06 (4.53)							4.31 (4.30)
Letrozole/Femara	0.76 (2.17)							1.35 (2.06)
Switched Between AIs	13.73 (2.90)**							12.65 (2.76)**
Switched Between AIs & Tamoxifen	24.96 (1.81)**							22.82 (1.73)**
Antidepressants		7.62 (1.49)**						0.75 (1.42)
Anticonvulsants			8.69 (1.56)**					1.44 (1.49)
Adrenals				10.96 (1.48)**				5.18 (1.40)**
Nonsteroidal anti-inflammatory agents					13.49 (1.44)**			8.22 (1.41)**
Anti-inflammatory agents						13.56 (1.61)**		7.58 (1.52)**
Vitamins (A, B, C, D, E, K, and/or multi)							10.99 (1.63)**	8.41 (1.50)**
R-squared	0.13	0.02	0.02	0.04	0.06	0.05	0.03	0.23
Adjusted R-squared	0.13	0.02	0.02	0.04	0.06	0.05	0.03	0.22
No. observations	1399	1399	1399	1399	1399	1399	1399	1399

Standard errors are reported in parentheses.

*Indicates significance at the 95% level.

Indicates significance at the 99% level.

Type of endocrine therapy – Tamoxifen and nonreceipt of medications through Medicaid were set as the reference groups for the models.

AI: aromatase inhibitor.

Next, all of the pharmaceutical variables were included in a regression model with ET usage duration as the dependent variable. See Table 1, Model H. The results showed that receipt of antidepressants and anticonvulsants was no longer significantly associated with ET usage duration when controlling for the other pharmaceutical variables. These variables were removed from the model. Interaction terms were generated between each pair of pharmaceutical variables and entered as a block in the model; however, only the interactions between ET type/adrenals (β = −2.5, p < 0.001) and anti-inflammatory agents/vitamins (β = −9.96, p = 0.04) were significant. The final model was developed and included ET type; receipt of the following concurrent prescriptions: adrenals, nonsteroidal anti-inflammatory agents, anti-inflammatory agents, and/or vitamins; and anti-inflammatory agents/vitamins and ET type/adrenals interactions (see Table 2).

Table 2.

Multiple regression results for variables associated with endocrine therapy usage duration for the South Carolina Medicaid Population, 2000–2012 (final model).

Variables	Coefficient	Standard error	p-Value
Intercept	14.06	1.68	<0.001
Endocrine therapy type – Anastrozole/Arimidex	12.20	3.24	<0.001
Endocrine therapy type – Exemestane/Aromasin	4.63	5.48	0.398
Endocrine therapy type – Letrozole/Femara	8.88	3.02	0.003
Endocrine therapy type – switched between AIs	23.58	5.47	<0.001
Endocrine therapy type – switched between Tamoxifen and AIs	29.27	2.85	<0.001
Receipt of adrenals prescription	10.90	2.04	<0.001
Receipt of nonsteroidal anti-inflammatory agents prescription	8.46	1.38	<0.001
Receipt of anti-inflammatory agents prescription	9.91	1.81	<0.001
Receipt of vitamins prescription	11.24	1.80	<0.001
Endocrine therapy type * Adrenals
Anastrozole/Arimidex	−5.32	4.11	0.196
Exemestane/Aromasin	0.75	8.75	0.932
Letrozole/Femara	−13.66	4.09	0.001
Switched between AIs	−15.50	6.33	0.014
Switched between Tamoxifen and AIs	−10.33	3.56	0.004
Anti-inflammatory agents * Vitamins	−7.06	3.13	0.024

N = 1399; R² = 0.23; Adj R² = 0.22.

Endocrine therapy type – Tamoxifen was set as the reference group.

AIs: aromatase inhibitors.

Discussion

Our study found that none of the demographic or clinical factors examined were significantly associated with an individual's ET usage duration. The sample's socioeconomic and age (<64) homogeneity possibly overwhelmed differences in race, marital status, or rural/urban residency status, or as other studies have shown, side-effect management may be more impactful than demographic or clinical aspects.^13–17,35

Similarly, Friese et al.³⁶ found that race, SEER stage, worry about recurrence, and primary oncology provider were not significantly associated with ET usage in a population of Los Angeles County and Detroit metropolitan area breast cancer survivors; however, age and taking two or more medications weekly were significantly associated with greater ET persistence. Women ages 20–79 were included in the Friese et al.'s³⁶ study. Calip et al.³⁷ also found that in a sample of 40,009 women, increasing polypharmacy and pill burden were associated with greater ET adherence, but different effects were found depending on the medication class. For example, lipid-lowering drugs and antihypertensives were associated with higher adherence, and opioid-containing analgesics, anxiolytics/antipsychotics, antidepressants, and insulin therapy were associated with lower adherence.³⁷

Our study highlights the association between ET usage duration with ET type and with other prescriptions that were possibly prescribed for side-effect management. The final model included ET type and receipt of certain prescriptions, which can be used to alleviate common side-effects of Tamoxifen and aromatase inhibitors: adrenals, nonsteroidal anti-inflammatory agents, anti-inflammatory agents, and vitamins.

The model showed that the average ET duration was 14 months for women meeting the sample inclusion criteria, taking Tamoxifen, and who had not filled a prescription for any of the following: adrenals, nonsteroidal anti-inflammatory agents, anti-inflammatory agents, and/or vitamins. Taking Anastrozole/Arimidex significantly increased ET usage duration by an average of 12.2 months over the duration for Tamoxifen, and taking Letrozole/Femara significantly increased duration by 8.9 months. Women who switched between different aromatase inhibitors or between Tamoxifen and aromatase inhibitors took ET for an average of 23.6 or 29.3 months longer, respectively, than Tamoxifen-only users. Having the following prescriptions was also significantly associated with increased ET duration: adrenals (+10.9 months), nonsteroidal anti-inflammatory agents (+8.5 months), anti-inflammatory agents (+9.9 months), and vitamins (+11.24 months). As shown by the interaction terms in Table 2, the results are not additive for survivors taking adrenals in combination with Letrozole/Femara, switching between aromatase inhibitors, or switching between Tamoxifen and aromatase inhibitors; or for survivors taking anti-inflammatory agents with vitamins.

The literature contains many studies on subpopulations affected by low rates of ET usage. This study helps fill a gap in the literature regarding factors positively associated with ET usage duration among the socioeconomically disadvantaged that could potentially be used to better emerging interventions. The most effective methods for these necessary interventions are still under development, and there is a gap in the literature regarding the optimal timing for intervention. This study identifies that demographic and clinical factors were not associated with ET usage duration for this population; however, ET type and having prescriptions for drugs commonly known to alleviate side-effects was significantly associated.

This analysis should be viewed as a hypothesis-generating study and can be used to further investigate the relationship between ET type and other prescriptions taken with ET with ET usage duration. The variables significantly associated with ET usage duration explain 23% of the variance in ET usage duration among the sample, so further investigation is warranted to determine other associated factors. The purpose of the additional prescriptions was unknown, so it is also not known if these prescriptions were written to specifically alleviate side-effects or for other purposes. Next steps would include looking at the timing of side-effect prescriptions and ET medications. Dosage and usage patterns of other prescriptions were also not examined, only that the individual filled at least one prescription for the medication during the study period. Furthermore, over-the-counter NSAIDS or vitamins could not be accounted for due to the nature of Medicaid prescription claims data.

Conclusion

This study focused on South Carolina Medicaid recipients who were hormone receptor-positive breast cancer survivors. The results of this study point to an effective point of intervention before 14 months for ET initiators who meet the sample inclusion criteria and that ET type and other prescriptions taken by survivors are more important for increasing the length of ET duration than the demographic and clinical factors examined. Further research is warranted to test these findings in other populations. Further research is also needed to test pharmacologic intervention strategies associated with longer ET duration in this study in addition to other nonpharmacologic interventions among low income populations.³⁸

Interventions aimed at enhancing the ET experience for breast cancer survivors to increase disease-free survival and quality of life are an immediate need. The results of this study can be seen as an important first step at examining factors associated with longer ET usage.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

References

Early Breast Cancer Trialists' Collaborative Group. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 365: 1687–1717.

Reynolds

Higgins

. Endocrine therapy for breast cancer: a tough pill to swallow. Menopause 2013; 20: 714–716.

Murphy

Bartholomew

Carpentier

, et al. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat 2012; 134: 459–478.

Yung

Hassett

Chen

, et al. Initiation of adjuvant hormone therapy by Medicaid insured women with nonmetastatic breast cancer. J Natl Cancer Inst 2012; 104: 1102–1105.

Wagner

Jing

Boscoe

, et al. Improving adjuvant hormone therapy use in Medicaid managed care–insured women, New York State, 2012–2014. Prev Chronic Dis 2016; 13: 160185.

Wheeler

Kohler

Reeder-Hayes

, et al. Endocrine therapy initiation among Medicaid-insured breast cancer survivors with hormone receptor-positive tumors. J Cancer Surviv 2014; 8: 603–610.

Gotay

Dunn

. Adherence to long-term adjuvant hormonal therapy for breast cancer. Expert Rev Pharmacoecon Outcomes Res 2011; 11: 709–715.

Chlebowski

Kim

Haque

. Adherence to endocrine therapy in breast cancer adjuvant and prevention settings. Cancer Prev Res 2014; 7: 378–387.

Hurtado-de-Mendoza

Cabling

Lobo

, et al. Behavioral interventions to enhance adherence to hormonal therapy in breast cancer survivors: a systematic literature review. Clin Breast Cancer 2016; 16: 247–255.e3.

10.

Crew

Capodice

Greenlee

, et al. Randomized, blinded, sham-controlled trial of acupuncture for the management of aromatase inhibitor–associated joint symptoms in women with early-stage breast cancer. J Clin Oncol 2010; 28: 1154–1160.

11.

Irwin

Cartmel

Gross

, et al. Randomized exercise trial of aromatase inhibitor–induced arthralgia in breast cancer survivors. J Clin Oncol 2015; 33: 1104–1111.

12.

Khan

Reddy

Kimler

, et al. Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer. Breast Cancer Res Treat 2010; 119: 111–118.

13.

Wagner

Zhao

Goss

, et al. Patient-reported predictors of early treatment discontinuation: treatment-related symptoms and health-related quality of life among postmenopausal women with primary breast cancer randomized to anastrozole or exemestane on NCIC Clinical Trials Group (CCTG) MA. 27 (E1Z03). Breast Cancer Res 2018; 169: 537–548.

14.

Paul M. Why women quit breast cancer drugs early: side effects are so bad women end treatment and risk return of cancer. Northwestern University. http://www.northwestern.edu/newscenter/stories/2011/12/breast-cancer-d.html (accessed 7 March 2018).

15.

Bluethmann

Murphy

Tiro

, et al. Deconstructing decisions to initiate, maintain, or discontinue adjuvant endocrine therapy in breast cancer survivors: a mixed-methods study. Oncol Nurs Forum 2017; 44: E101–E110.

16.

Wheeler

Roberts

Bloom

, et al. Oncology providers' perspectives on endocrine therapy prescribing and management. Patient Prefer Adherence 2016; 10: 2007–2019.

17.

Wells

Pan

Vázquez-Otero

, et al. Barriers and facilitators to endocrine therapy adherence among underserved hormone-receptor positive breast cancer survivors: a qualitative study. Support Care Cancer 2016; 24: 4123–4130.

18.

Barton

Sloan

Shuster

, et al. Evaluating the efficacy of vaginal dehydroepiandosterone for vaginal symptoms in postmenopausal cancer survivors: NCCTG N10C1 (Alliance). Support Care Cancer 2018; 26: 643–650.

19.

Marshall-McKenna

Morrison

Stirling

, et al. A randomised trial of the cool pad pillow topper versus standard care for sleep disturbance and hot flushes in women on endocrine therapy for breast cancer. Support Care in Cancer 2016; 24: 1821–1829.

20.

Chan

De Boer

Gan

, et al. Randomized phase II placebo-controlled study to evaluate the efficacy of topical pure emu oil for joint pain related to adjuvant aromatase inhibitor use in postmenopausal women with early breast cancer: JUST (Joints Under Study). Support Care Cancer 2017; 25: 3785–3791.

21.

Ekinci

Nathoo

Korattyil

, et al.

Interventions to improve endocrine therapy adherence in breast cancer survivors: what is the evidence?

J Cancer Surviv 2018; 12: 348–356.

22.

Doggrell

. Adherence to oral endocrine treatments in women with breast cancer: can it be improved? Breast Cancer Res Treat 2011; 129: 299–308.

23.

L'Espérance

Frenette

Dionne

, et al. Pharmacological and non-hormonal treatment of hot flashes in breast cancer survivors: CEPO review and recommendations. Support Care Cancer 2013; 21: 1461–1474.

24.

Gainford

Simmons

Nguyen

, et al. A practical guide to the management of menopausal symptoms in breast cancer patients. Support Care Cancer 2005; 13: 573–578.

25.

Kubo

Onishi

Kuroki

, et al. Short-term and low-dose prednisolone administration reduces aromatase inhibitor-induced arthralgia in patients with breast cancer. Anticancer Res 2012; 32: 2331–2336.

26.

Younus

Kligman

. Management of aromatase inhibitor–induced arthralgia. Curr Oncol Rep 2010; 17: 87.

27.

Dent

Gaspo

Kissner

, et al. Aromatase inhibitor therapy: toxicities and management strategies in the treatment of postmenopausal women with hormone-sensitive early breast cancer. Breast Cancer Res Treat 2011; 126: 295–310.

28.

Denlinger C, et al. NCCN Clinical Practice Guidelines in Oncology: Survivorship. National Comprehensive Cancer Network. https://www.nccn.org/professionals/physician_gls/pdf/survivorship.pdf (accessed 29 March 2018).

29.

South Carolina Central Cancer Registry (SCCCR), Division of Public Health Statistics and Information Services, South Carolina Department of Health and Environmental Control. http://www.scdhec.gov/Health/DiseasesandConditions/Cancer/CancerStatisticsReports/CancerRegistry/ (accessed 7 March 2018).

30.

Helwick C. Benefit of extended adjuvant endocrine therapy not upheld in multiple studies reported in San Antonio. American Society of Clinical Oncology. http://www.ascopost.com/issues/december-25-2016/benefit-of-extended-adjuvant-endocrine-therapy-not-upheld-in-multiple-studies-reported-in-san-antonio/ (accessed 3 March 2018).

31.

Goodman A. Extended endocrine therapy in postmenopausal women with breast cancer: 2 years as effective as 5 years. American Society of Clinical Oncology. http://www.ascopost.com/issues/december-25-2017/extended-endocrine-therapy-in-postmenopausal-women-with-breast-cancer-2-years-as-effective-as-5-years/ (accessed 5 March 2018).

32.

Burstein

Temin

Anderson

, et al. Adjuvant endocrine therapy for women with hormone receptor–positive breast cancer: American Society of Clinical Oncology clinical practice guideline focused update. J Clin Oncol 2014; 32: 2255–2269.

33.

ASCO guideline update recommends tamoxifen for up to 10 years for women with non-metastatic hormone receptor positive breast cancer. American Society of Clinical Oncology. https://www.asco.org/about-asco/press-center/news-releases/asco-guideline-update-recommends-tamoxifen-10-years-women-non (accessed 5 March 2018).

34.

Hormonal therapy for early-stage hormone receptor-positive breast cancer. American Society of Clinical Oncology. http://www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/hormonal-therapy-early-stage-hormone-receptor-positive-breast-cancer (accessed 3 March 2018).

35.

Felder

, et al. Racial differences in receipt of adjuvant hormonal therapy among Medicaid enrollees in South Carolina diagnosed with breast cancer. Breast Cancer Res Treat 2016; 157: 193–200.

36.

Friese

Pini

, et al. Adjuvant endocrine therapy initiation and persistence in a diverse sample of patients with breast cancer. Breast Cancer Res Treat 2013; 138: 931–939.

37.

Calip

Xing

Jun

, et al. Polypharmacy and adherence to adjuvant endocrine therapy for breast cancer. J Oncol Pract 2017; 13: e451–e462.

38.

David

Fallowfield

. Recognition and management of treatment-related side effects for breast cancer patients receiving adjuvant endocrine therapy. Breast Cancer Res Treat 2008; 107: 167–180.