Factors associated with initiation and continuation of endocrine therapy in women with hormone receptor-positive breast cancer

Beomyoung Cho, Maria Pérez, Donna B Jeffe, Matthew W Kreuter, Julie A Margenthaler, Graham A Colditz, Ying Liu, Beomyoung Cho, Maria Pérez, Donna B Jeffe, Matthew W Kreuter, Julie A Margenthaler, Graham A Colditz, Ying Liu

Abstract

Background: Despite benefits of endocrine therapy (ET) for patients with hormone-receptor (HR)-positive breast cancer, many patients do not initiate or discontinue ET against recommendations.

Methods: We identified variables associated with ET initiation and continuation, analyzing pooled data from two longitudinal studies at a National Cancer Institute comprehensive cancer center in St. Louis, Missouri. The sample included 533 women with newly diagnosed, non-metastatic, HR-positive breast cancer who completed interviews at enrollment and 6, 12, and 24 months after definitive surgical treatment. Logistic regression models estimated the adjusted odds ratio and 95% confidence interval (aOR [95% CI]) for each of self-reported ET initiation by the 12-month interview and continuation for ≥12 months by the 24-month interview in association with self-reported diabetes, elevated depressed mood, menopausal-symptom severity and obesity, adjusting for race, age, insurance status, chemotherapy, and radiation therapy.

Results: Overall, 81.4% (434/533) of patients initiated ET, and 86.5% (371/429) continued ET ≥12 months. Patients with diabetes had lower odds of initiating ET (0.50 [0.27-0.91]). Patients reporting greater menopausal-symptom severity had lower odds of continuing ET (0.72 [0.53-0.99]).

Conclusion: Efforts to increase ET initiation among patients with diabetes and better manage severe menopausal symptoms among ET users might promote ET continuation.

Clinical trial information: ClinicalTrials.gov : #NCT00929084.

Keywords: Breast cancer; Depression; Diabetes; Hormone therapy; Menopausal symptoms; Obesity.

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Inclusion/exclusion procedure of study sample

References

    1. American Cancer Society . Breast Cancer Facts & Figures 2019-2020. Atlanta: American Cancer Society, Inc.; 2019.
    1. Farias AJ, Du XL. Racial differences in adjuvant endocrine therapy use and discontinuation in association with mortality among Medicare breast Cancer patients by receptor status. Cancer Epidemiol Biomark Prev. 2017;26(8):1266–1275. doi: 10.1158/1055-9965.EPI-17-0280.
    1. Wheeler SB, Kohler RE, Reeder-Hayes KE, Goyal RK, Lich KH, Moore A, Smith TW, Melvin CL, Muss HB. Endocrine therapy initiation among Medicaid-insured breast cancer survivors with hormone receptor-positive tumors. J Cancer Surviv. 2014;8(4):603–610. doi: 10.1007/s11764-014-0365-3.
    1. Livaudais JC, Hershman DL, Habel L, Kushi L, Gomez SL, Li CI, Neugut AI, Fehrenbacher L, Thompson B, Coronado GD. Racial/ethnic differences in initiation of adjuvant hormonal therapy among women with hormone receptor-positive breast cancer. Breast Cancer Res Treat. 2012;131(2):607–617. doi: 10.1007/s10549-011-1762-1.
    1. Hershman DL, Kushi LH, Shao T, Buono D, Kershenbaum A, Tsai WY, Fehrenbacher L, Gomez SL, Miles S, Neugut AI. Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol. 2010;28(27):4120–4128. doi: 10.1200/JCO.2009.25.9655.
    1. Haskins CB, McDowell BD, Carnahan RM, Fiedorowicz JG, Wallace RB, Smith BJ, Chrischilles EA. Impact of preexisting mental illness on breast cancer endocrine therapy adherence. Breast Cancer Res Treat. 2019;174(1):197–208. doi: 10.1007/s10549-018-5050-1.
    1. Hershman DL, Shao T, Kushi LH, Buono D, Tsai WY, Fehrenbacher L, Kwan M, Gomez SL, Neugut AI. Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer. Breast Cancer Res Treat. 2011;126(2):529–537. doi: 10.1007/s10549-010-1132-4.
    1. Freedman RA, Virgo KS, He Y, Pavluck AL, Winer EP, Ward EM, Keating NL. The association of race/ethnicity, insurance status, and socioeconomic factors with breast cancer care. Cancer. 2011;117(1):180–189. doi: 10.1002/cncr.25542.
    1. Lega IC, Austin PC, Fischer HD, Fung K, Krzyzanowska MK, Amir E, Lipscombe LL. The impact of diabetes on breast Cancer treatments and outcomes: a population-based study. Diabetes Care. 2018;41(4):755–761. doi: 10.2337/dc17-2012.
    1. Richardson LC, Pollack LA. Therapy insight: influence of type 2 diabetes on the development, treatment and outcomes of cancer. Nat Clin Pract Oncol. 2005;2(1):48–53. doi: 10.1038/ncponc0062.
    1. van de Poll-Franse LV, Houterman S, Janssen-Heijnen ML, Dercksen MW, Coebergh JW, Haak HR. Less aggressive treatment and worse overall survival in cancer patients with diabetes: a large population based analysis. Int J Cancer. 2007;120(9):1986–1992. doi: 10.1002/ijc.22532.
    1. He W, Fang F, Varnum C, Eriksson M, Hall P, Czene K. Predictors of discontinuation of adjuvant hormone therapy in patients with breast Cancer. J Clin Oncol. 2015;33(20):2262–2269. doi: 10.1200/JCO.2014.59.3673.
    1. Mausbach BT, Schwab RB, Irwin SA. Depression as a predictor of adherence to adjuvant endocrine therapy (AET) in women with breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat. 2015;152(2):239–246. doi: 10.1007/s10549-015-3471-7.
    1. Kidwell KM, Harte SE, Hayes DF, Storniolo AM, Carpenter J, Flockhart DA, Stearns V, Clauw DJ, Williams DA, Henry NL. Patient-reported symptoms and discontinuation of adjuvant aromatase inhibitor therapy. Cancer. 2014;120(16):2403–2411. doi: 10.1002/cncr.28756.
    1. Kemp A, Preen DB, Saunders C, Boyle F, Bulsara M, Malacova E, Roughead EE. Early discontinuation of endocrine therapy for breast Cancer: who is at risk in clinical practice? SpringerPlus. 2014;3(1):282–291. doi: 10.1186/2193-1801-3-282.
    1. Cluze C, Rey D, Huiart L, BenDiane MK, Bouhnik AD, Berenger C, Carrieri MP, Giorgi R. Adjuvant endocrine therapy with tamoxifen in young women with breast cancer: determinants of interruptions vary over time. Ann Oncol. 2012;23(4):882–890. doi: 10.1093/annonc/mdr330.
    1. Stanton AL, Petrie KJ, Partridge AH. Contributors to nonadherence and nonpersistence with endocrine therapy in breast cancer survivors recruited from an online research registry. Breast Cancer Res Treat. 2014;145(2):525–534. doi: 10.1007/s10549-014-2961-3.
    1. Fu MR, Axelrod D, Guth AA, Cleland CM, Ryan CE, Weaver KR, Qiu JM, Kleinman R, Scagliola J, Palamar JJ, et al. Comorbidities and quality of life among breast Cancer survivors: a prospective study. J Pers Med. 2015;5(3):229–242. doi: 10.3390/jpm5030229.
    1. Edgington A, Morgan MA. Looking beyond recurrence: comorbidities in cancer survivors. Clin J Oncol Nurs. 2011;15(1):E3–12. doi: 10.1188/11.CJON.E3-E12.
    1. Lee K, Kruper L, Dieli-Conwright CM, Mortimer JE. The impact of obesity on breast Cancer diagnosis and treatment. Curr Oncol Rep. 2019;21(5):41. doi: 10.1007/s11912-019-0787-1.
    1. Goodwin PJ. Obesity and endocrine therapy: host factors and breast cancer outcome. Breast. 2013;22(Suppl 2):S44–S47. doi: 10.1016/j.breast.2013.07.008.
    1. Ewertz M, Jensen MB, Gunnarsdottir KA, Hojris I, Jakobsen EH, Nielsen D, Stenbygaard LE, Tange UB, Cold S. Effect of obesity on prognosis after early-stage breast cancer. J Clin Oncol. 2011;29(1):25–31. doi: 10.1200/JCO.2010.29.7614.
    1. Bernstein L, Deapen D, Cerhan JR, Schwartz SM, Liff J, McGann-Maloney E, Perlman JA, Ford L. Tamoxifen therapy for breast cancer and endometrial cancer risk. J Natl Cancer Inst. 1999;91(19):1654–1662. doi: 10.1093/jnci/91.19.1654.
    1. Chlebowski RT, Schottinger JE, Shi J, Chung J, Haque R. Aromatase inhibitors, tamoxifen, and endometrial cancer in breast cancer survivors. Cancer. 2015;121(13):2147–2155. doi: 10.1002/cncr.29332.
    1. Jeffe D, Pérez M, Liu Y, Collins K, Aft R, Schootman M. Quality of life over time in women diagnosed with ductal carcinoma in situ, early-stage invasive breast cancer, and age-matched controls. Breast Cancer Res Treat. 2012;134(1):379–391. doi: 10.1007/s10549-012-2048-y.
    1. Pérez M, Kreuter MW, Yan Y, Thompson T, Sefko J, Golla B, Margenthaler JA, Colditz G, Jeffe DB. Feasibility and acceptability of an interactive Cancer-communication video program using African American breast Cancer survivor stories. J Health Commun. 2020;25(7):566–575. doi: 10.1080/10810730.2020.1821132.
    1. Katzman R, Brown T, Fuld P, Peck A, Schechter R, Schimmel H. Validation of a short orientation-memory-concentration test of cognitive impairment. Am J Psychiatry. 1983.
    1. Pérez M, Sefko JA, Ksiazek D, Golla B, Casey C, Margenthaler JA, Colditz G, Kreuter MW, Jeffe DB. A novel intervention using interactive technology and personal narratives to reduce cancer disparities: African American breast cancer survivor stories. J Cancer Surviv. 2014;8(1):21–30. doi: 10.1007/s11764-013-0308-4.
    1. Thompson T, Pérez M, Yan Y, Kreuter MW, Margenthaler JA, Colditz GA, Jeffe DB. Randomized controlled trial of a breast cancer survivor stories intervention for African American women. Soc Sci Med. 2021;270:113663. doi: 10.1016/j.socscimed.2020.113663.
    1. Katz JN, Chang LC, Sangha O, Fossel AH, Bates DW. Can comorbidity be measured by questionnaire rather than medical record review? Med Care. 1996:73–84.
    1. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Clin Epidemiol. 1987;40(5):373–383.
    1. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33(1):159–174. doi: 10.2307/2529310.
    1. Okura Y, Urban LH, Mahoney DW, Jacobsen SJ, Rodeheffer RJ. Agreement between self-report questionnaires and medical record data was substantial for diabetes, hypertension, myocardial infarction and stroke but not for heart failure. J Clin Epidemiol. 2004;57(10):1096–1103. doi: 10.1016/j.jclinepi.2004.04.005.
    1. Tisnado DM, Adams JL, Liu H, Damberg CL, Chen WP, Hu FA, Carlisle DM, Mangione CM, Kahn KL. What is the concordance between the medical record and patient self-report as data sources for ambulatory care? Med Care. 2006;44(2):132–140. doi: 10.1097/.
    1. Kilbourne AM, Schumacher K, Frayne SM, Cypel Y, Barbaresso MM, Nord KM, Perzhinsky J, Lai Z, Prenovost K, Spiro A, et al. Physical health conditions among a population-based cohort of Vietnam-era women veterans: agreement between self-report and medical records. J Women's Health (Larchmt) 2017;26(11):1244–1251. doi: 10.1089/jwh.2016.6069.
    1. Simpson CF, Boyd CM, Carlson MC, Griswold ME, Guralnik JM, Fried LP. Agreement between self-report of disease diagnoses and medical record validation in disabled older women: factors that modify agreement. J Am Geriatr Soc. 2004;52(1):123–127. doi: 10.1111/j.1532-5415.2004.52021.x.
    1. Bush TL, Miller SR, Golden AL, Hale WE. Self-report and medical record report agreement of selected medical conditions in the elderly. Am J Public Health. 1989;79(11):1554–1556. doi: 10.2105/AJPH.79.11.1554.
    1. Centers for Disease Control Prevention . Overweight & obesity: defining adult overweight and obesity. In: United States; 2016.
    1. Radloff LS. The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas. 1977;1(3):385–401. doi: 10.1177/014662167700100306.
    1. Sawyer Radloff L, Teri L. Use of the center for epidemiological studies-depression scale with older adults. Clin Gerontol. 1986;5(1-2):119–136. doi: 10.1300/J018v05n01_06.
    1. Pérez M, Liu Y, Schootman M, Aft RL, Schechtman KB, Gillanders WE, Jeffe DB. Changes in sexual problems over time in women with and without early-stage breast cancer. Menopause. 2010;17(5):924. doi: 10.1097/gme.0b013e3181d5dd26.
    1. Perez M, Schootman M, Hall L, Jeffe D. Accelerated partial breast irradiation compared with whole breast radiation therapy: a breast cancer cohort study measuring change in radiation side-effects severity and quality of life. Breast Cancer Res Treat. 2017;162(2):329–342. doi: 10.1007/s10549-017-4121-z.
    1. Srokowski TP, Fang S, Hortobagyi GN, Giordano SH. Impact of diabetes mellitus on complications and outcomes of adjuvant chemotherapy in older patients with breast cancer. J Clin Oncol. 2009;27(13):2170–2176. doi: 10.1200/JCO.2008.17.5935.
    1. Shao S, Gill AA, Zahm SH, Jatoi I, Shriver CD, McGlynn KA, Zhu K. Diabetes and overall survival among breast Cancer patients in the U.S. military health system. Cancer Epidemiol Biomark Prev. 2018;27(1):50–57. doi: 10.1158/1055-9965.EPI-17-0439.
    1. Decker MR, Greenblatt DY, Havlena J, Wilke LG, Greenberg CC, Neuman HB. Impact of neoadjuvant chemotherapy on wound complications after breast surgery. Surgery. 2012;152(3):382–388. doi: 10.1016/j.surg.2012.05.001.
    1. Onitilo AA, Doi SA, Engel JM, Glurich I, Johnson J, Berg R. Clustering of venous thrombosis events at the start of tamoxifen therapy in breast cancer: a population-based experience. Thromb Res. 2012;130(1):27–31. doi: 10.1016/j.thromres.2011.11.025.
    1. Hernandez RK, Sørensen HT, Pedersen L, Jacobsen J, Lash TL. Tamoxifen treatment and risk of deep venous thrombosis and pulmonary embolism: a Danish population-based cohort study. Cancer: Interdisciplinary International Journal of the American Cancer Society. 2009;115(19):4442–4449. doi: 10.1002/cncr.24508.
    1. Fisher B, Costantino JP, Wickerham DL, Cecchini RS, Cronin WM, Robidoux A, Bevers TB, Kavanah MT, Atkins JN, Margolese RG. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and bowel project P-1 study. J Natl Cancer Inst. 2005;97(22):1652–1662. doi: 10.1093/jnci/dji372.
    1. Bronsveld HK, Jensen V, Vahl P, De Bruin ML, Cornelissen S, Sanders J, Auvinen A, Haukka J, Andersen M, Vestergaard P, et al. Diabetes and breast Cancer subtypes. PLoS One. 2017;12(1):e0170084. doi: 10.1371/journal.pone.0170084.
    1. Peairs KS, Barone BB, Snyder CF, Yeh HC, Stein KB, Derr RL, Brancati FL, Wolff AC. Diabetes mellitus and breast cancer outcomes: a systematic review and meta-analysis. J Clin Oncol. 2011;29(1):40–46. doi: 10.1200/JCO.2009.27.3011.
    1. Jarvandi S, Pérez M, Margenthaler J, Colditz GA, Kreuter MW, Jeffe DB. Improving lifestyle behaviors after breast Cancer treatment among African American women with and without diabetes: role of health care professionals. Ann Behav Med. 2020.
    1. Luo J, Hendryx M, Virnig B, Wen S, Chlebowski R, Chen C, Rohan T, Tinker L, Wactawski-Wende J, Lessin L. Pre-existing diabetes and breast cancer prognosis among elderly women. Br J Cancer. 2015;113(5):827–832. doi: 10.1038/bjc.2015.249.
    1. Jarvandi S, Pérez M, Schootman M, Jeffe DB. Pre-existing diabetes in early stage breast cancer patients is associated with lack of improvement in quality of life 2 years after diagnosis. Int J Behav Med. 2016;23(6):722–729. doi: 10.1007/s12529-016-9577-4.
    1. Bluethmann SM, Murphy CC, Tiro JA, Mollica MA, Vernon SW, Bartholomew LK. Deconstructing decisions to initiate, maintain, or discontinue adjuvant endocrine therapy in breast Cancer survivors: a mixed-methods study. Oncol Nurs Forum. 2017;44(3):E101–e110. doi: 10.1188/17.ONF.E101-E110.
    1. Chen Y, Dorjgochoo T, Bao PP, Zheng Y, Cai H, Lu W, Shu XO. Menopausal symptoms among breast cancer patients: a potential indicator of favorable prognosis. PLoS One. 2013;8(9):e75926. doi: 10.1371/journal.pone.0075926.
    1. Glaus A, Boehme C, Thurlimann B, Ruhstaller T, Hsu Schmitz SF, Morant R, Senn HJ, von Moos R. Fatigue and menopausal symptoms in women with breast cancer undergoing hormonal cancer treatment. Ann Oncol. 2006;17(5):801–806. doi: 10.1093/annonc/mdl030.
    1. Harris PF, Remington PL, Trentham-Dietz A, Allen CI, Newcomb PA. Prevalence and treatment of menopausal symptoms among breast cancer survivors. J Pain Symptom Manag. 2002;23(6):501–509. doi: 10.1016/S0885-3924(02)00395-0.
    1. Wagner LI, Zhao F, Goss PE, Chapman J-AW, Shepherd LE, Whelan TJ, Mattar BI, Bufill JA, Schultz WC, LaFrancis IE, 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 Treat. 2018;169(3):537–548. doi: 10.1007/s10549-018-4713-2.
    1. Wheeler SB, Roberts MC, Bloom D, Reeder-Hayes KE, Espada M, Peppercorn J, Golin CE, Earp JA. Oncology providers' perspectives on endocrine therapy prescribing and management. Patient preference and adherence. 2016;10:2007–2019. doi: 10.2147/PPA.S95594.
    1. Wells KJ, Pan TM, Vázquez-Otero C, Ung D, Ustjanauskas AE, Muñoz D, Laronga C, Roetzheim RG, Goldenstein M, Carrizosa C, 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(10):4123–4130. doi: 10.1007/s00520-016-3229-8.
    1. Fontein D, Seynaeve C, Hadji P, Hille E, van de Water W, Putter H, Kranenbarg E, Hasenburg A, Paridaens RJ, Vannetzel J-M. Specific adverse events predict survival benefit in patients treated with tamoxifen or aromatase inhibitors: an international tamoxifen exemestane adjuvant multinational trial analysis. J Clin Oncol. 2013;31(18):2257–2264. doi: 10.1200/JCO.2012.45.3068.
    1. Fontein D, Houtsma D, Hille E, Seynaeve C, Putter H, Meershoek-Klein Kranenbarg E, Guchelaar HJ, Gelderblom H, Dirix L, Paridaens R. Relationship between specific adverse events and efficacy of exemestane therapy in early postmenopausal breast cancer patients. Ann Oncol. 2012;23(12):3091–3097. doi: 10.1093/annonc/mds204.
    1. Cusack L, Brennan M, Baber R, Boyle F. Menopausal symptoms in breast cancer survivors: management update. Br J Gen Pract. 2013;63(606):51–52. doi: 10.3399/bjgp13X660977.
    1. Deng G, Vickers A, Yeung S, D'Andrea GM, Xiao H, Heerdt AS, Sugarman S, Troso-Sandoval T, Seidman AD, Hudis CA, et al. Randomized, controlled trial of acupuncture for the treatment of hot flashes in breast cancer patients. J Clin Oncol. 2007;25(35):5584–5590. doi: 10.1200/JCO.2007.12.0774.
    1. Bokmand S, Flyger H. Acupuncture relieves menopausal discomfort in breast cancer patients: a prospective, double blinded, randomized study. Breast. 2013;22(3):320–323. doi: 10.1016/j.breast.2012.07.015.
    1. Lesi G, Razzini G, Musti MA, Stivanello E, Petrucci C, Benedetti B, Rondini E, Ligabue MB, Scaltriti L, Botti A, et al. Acupuncture as an integrative approach for the treatment of hot flashes in women with breast Cancer: a prospective multicenter randomized controlled trial (AcCliMaT) J Clin Oncol. 2016;34(15):1795–1802. doi: 10.1200/JCO.2015.63.2893.
    1. Hickey M, Szabo RA, Hunter MS. Non-hormonal treatments for menopausal symptoms. Bmj. 2017;359:j5101. doi: 10.1136/bmj.j5101.
    1. Chan CW, Tai D, Kwong S, Chow KM, Chan DN, Law BM. The effects of pharmacological and non-pharmacological interventions on symptom management and quality of life among breast cancer survivors undergoing adjuvant endocrine therapy: a systematic review. Int J Environ Res Public Health. 2020;17(8):2950. doi: 10.3390/ijerph17082950.
    1. Franzoi MA, Agostinetto E, Perachino M, Del Mastro L, de Azambuja E, Vaz-Luis I, Partridge AH, Lambertini M. Evidence-based approaches for the management of side-effects of adjuvant endocrine therapy in patients with breast cancer. The Lancet Oncology. 2021;22(7):e303–e313. doi: 10.1016/S1470-2045(20)30666-5.
    1. Henry NL, Azzouz F, Desta Z, Li L, Nguyen AT, Lemler S, Hayden J, Tarpinian K, Yakim E, Flockhart DA, et al. Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer. J Clin Oncol. 2012;30(9):936–942. doi: 10.1200/JCO.2011.38.0261.
    1. Krebber AM, Buffart LM, Kleijn G, Riepma IC, de Bree R, Leemans CR, Becker A, Brug J, van Straten A, Cuijpers P, et al. Prevalence of depression in cancer patients: a meta-analysis of diagnostic interviews and self-report instruments. Psychooncology. 2014;23(2):121–130. doi: 10.1002/pon.3409.
    1. Lingam R, Scott J. Treatment non-adherence in affective disorders. Acta Psychiatr Scand. 2002;105(3):164–172. doi: 10.1034/j.1600-0447.2002.1r084.x.
    1. Riley GF, Warren JL, Harlan LC, Blackwell SA. Endocrine therapy use among elderly hormone receptor-positive breast cancer patients enrolled in Medicare part D. Medicare Medicaid Res Rev. 2011;1(4).
    1. Thompson T, Rodebaugh TL, Pérez M, Struthers J, Sefko JA, Lian M, Schootman M, Jeffe DB. Influence of neighborhood-level factors on social support in early-stage breast cancer patients and controls. Soc Sci Med. 2016;156:55–63. doi: 10.1016/j.socscimed.2016.03.023.
    1. Friese CR, Pini TM, Li Y, Abrahamse PH, Graff JJ, Hamilton AS, Jagsi R, Janz NK, Hawley ST, Katz SJ, et al. Adjuvant endocrine therapy initiation and persistence in a diverse sample of patients with breast cancer. Breast Cancer Res Treat. 2013;138(3):931–939. doi: 10.1007/s10549-013-2499-9.
    1. Erickson K, Patterson RE, Flatt SW, Natarajan L, Parker BA, Heath DD, Laughlin GA, Saquib N, Rock CL, Pierce JP. Clinically defined type 2 diabetes mellitus and prognosis in early-stage breast cancer. J Clin Oncol. 2011;29(1):54. doi: 10.1200/JCO.2010.29.3183.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever