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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2017

01-10-2017 | Epidemiology

Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance)

Authors: Shirley M. Bluethmann, Catherine M. Alfano, Jonathan D. Clapp, George Luta, Brent J. Small, Arti Hurria, Harvey J. Cohen, Steven Sugarman, Hyman B. Muss, Claudine Isaacs, Jeanne S. Mandelblatt

Published in: Breast Cancer Research and Treatment | Issue 3/2017

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Abstract

Purpose

To investigate the effects of cognitive function on discontinuation of hormonal therapy in breast cancer survivors ages 65+ (“older”).

Methods

Older breast cancer survivors with invasive, non-metastatic disease, and no reported cognitive difficulties were recruited from 78 Alliance sites between 2004 and 2011. Eligible survivors (n = 1280) completed baseline interviews; follow-up was conducted annually for up to 7 years. Survivors with estrogen-receptor-positive (ER+) cancers who initiated hormonal therapy (n = 990) were included. Self-reported cognitive function was measured using the EORTC-QLQ30 scale; a difference of eight points on the 0–100 scale was considered clinically significant. Based on varying rates of discontinuation over time, discontinuation was evaluated separately for three time periods: early (<1 year); midpoint (1–3 years); and late discontinuation (>3–5 years). Cox models for each time period were used to evaluate the effects of cognition immediately preceding discontinuation, controlling for age, chemotherapy, and other covariates.

Results

Survivors were 65–91 years old (mean 72.6 years), and 79% had stages 1 or 2A disease. Overall, 43% discontinued hormonal therapy before 5 years. Survivors who reported lower cognitive function in the period before discontinuation had greater hazards of discontinuing therapy at the treatment midpoint (HR 1.22 per 8-point difference, CI 1.09–1.40, p < 0.001), considering covariates, but cognition was not related to discontinuation in the other periods.

Conclusions

Self-reported cognitive problems were a significant risk factor for discontinuation of hormonal therapy 1–3 years post-initiation. Additional research is needed on the temporality of cognitive effects and hormonal therapy to support survivorship care needs of older survivors.
Literature
1.
Chlebowski RT, Geller ML (2006) Adherence to endocrine therapy for breast cancer. Oncology 71:1–9CrossRef
2.
Chlebowski RT, Kim J, Haque R (2014) Adherence to endocrine therapy in breast cancer adjuvant and prevention settings. Cancer Prev Res 7:378–387CrossRef
3.
Gray RG, Rea D, Handley K et al (2013) aTTom: long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,953 women with early breast cancer. J Clin Oncol 31:5CrossRef
4.
Arimidex, Tamoxifen, Alone or in Combination Trialists’ Group, Buzdar A, Howell A et al (2006) Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Lancet Oncol 7:633–643CrossRef
5.
Murphy CC, Bartholomew LK, Carpentier MY et al (2012) Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat 134:459–478CrossRef
6.
Burstein HJ, Prestrud AA, Seidenfeld J et al (2010) American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol 28:3784–3796CrossRef
7.
Burstein HJ, Temin S, Anderson H et al (2014) Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline focused update. J Clin Oncol 32:2255–2269CrossRef
8.
Hershman DL, Kushi LH, Shao T et al (2010) Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol 28:4120–4128CrossRef
9.
Hershman DL (2013) Disparities and challenges in adherence to oral antineoplastic agents
10.
Bluethmann SM, Murphy CC, Tiro JA et al (2017) Deconstructing decisions to initiate, maintain, or discontinue adjuvant endocrine therapy in breast cancer survivors: a mixed-methods study. Oncol Nurs Forum 44(3):E101–E110CrossRef
11.
Stanton AL, Petrie KJ, Partridge AH (2014) Contributors to nonadherence and nonpersistence with endocrine therapy in breast cancer survivors recruited from an online research registry. Breast Cancer Res Treat 145:525–534CrossRef
12.
Lange M, Rigal O, Clarisse B et al (2014) Cognitive dysfunctions in elderly cancer patients: a new challenge for oncologists. Cancer Treat Rev 40:810–817CrossRef
13.
Karuturi M, Wong ML, Hsu T et al (2016) Understanding cognition in older patients with cancer. J Geriatr Oncol 7:258–269CrossRef
14.
Jenkins V, Shilling V, Deutsch G et al (2006) A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer. Br J Cancer 94:828–834CrossRef
15.
Agrawal K, Onami S, Mortimer JE et al (2010) Cognitive changes associated with endocrine therapy for breast cancer. Maturitas 67:209–214CrossRef
16.
Ganz PA, Kwan L, Castellon SA et al (2013) Cognitive complaints after breast cancer treatments: examining the relationship with neuropsychological test performance. J Natl Cancer Inst 105:791–801CrossRef
17.
Bellury L, Ellington L, Beck SL et al (2013) Older breast cancer survivors: can interaction analyses identify vulnerable subgroups? A report from the American Cancer Society Studies of Cancer Survivors. 40
18.
Bailey M, Wang AC, Hao J et al (2011) Interactive effects of age and estrogen on cortical neurons: implications for cognitive aging. Neuroscience 191:148–158CrossRef
19.
Phillips K, Aldridge J, Ribi K et al (2011) Cognitive function in postmenopausal breast cancer patients one year after completing adjuvant endocrine therapy with letrozole and/or tamoxifen in the BIG 1-98 trial. Breast Cancer Res Treat 126:221–226CrossRef
20.
Bender CM, Merriman JD, Gentry AL et al (2015) Patterns of change in cognitive function with anastrozole therapy. Cancer 121:2627–2636CrossRef
21.
Bluethmann SM, Mariotto AB, Rowland JH (2016) Anticipating the “Silver Tsunami”: prevalence trajectories and comorbidity burden among older cancer survivors in the United States. Cancer Epidemiol Biomark Prev 25:1029–1036CrossRef
22.
Mandelblatt JS, Sheppard VB, Hurria A et al (2010) Breast cancer adjuvant chemotherapy decisions in older women: the role of patient preference and interactions with physicians. J Clin Oncol 28:3146–3153CrossRef
23.
Mandelblatt JS, Faul LA, Luta G et al (2012) Patient and physician decision styles and breast cancer chemotherapy use in older women: cancer and leukemia group B protocol 369901. J Clin Oncol 30:2609–2614CrossRef
24.
Davis PB, Morris JC, Grant E (1990) Brief screening tests versus clinical staging in senile dementia of the Alzheimer type. J Am Geriatr Soc 38:129–135CrossRef
25.
Kawas C, Karagiozis H, Resau L et al (1995) Reliability of the blessed telephone information-memory-concentration test. J Geriatr Psychiatry Neurol 8:238–242CrossRef
26.
Aaronson NK, Ahmedzai S, Bergman B et al (1993) The European organization for research and treatment of cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85:365–376CrossRef
27.
Lash TL, Fox MP, Westrup JL et al (2006) Adherence to tamoxifen over the five-year course. Breast Cancer Res Treat 99:215–220CrossRef
28.
Searle SD, Mitnitski A, Gahbauer EA et al (2008) A standard procedure for creating a frailty index. BMC Geriatr 8:24CrossRef
29.
Rockwood K, Mitnitski A, Song X et al (2006) Long-term risks of death and institutionalization of elderly people in relation to deficit accumulation at age 70. J Am Geriatr Soc 54:975–979CrossRef
30.
Sheppard VB, Faul LA, Luta G et al (2014) Frailty and adherence to adjuvant hormonal therapy in older women with breast cancer: CALGB protocol 369901. J Clin Oncol 32:2318–2327CrossRef
31.
Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRef
32.
Bender CM, Sereika SM, Brufsky AM et al (2007) Memory impairments with adjuvant anastrozole versus tamoxifen in women with early-stage breast cancer. Menopause 14:995–998CrossRef
33.
Cox D (1972) Regression Models and Life-Tables. Journal of the Royal Statistical Society. Series B (Methodological) 34:187–220CrossRef
34.
He W, Fang F, Varnum C et al (2015) Predictors of discontinuation of adjuvant hormone therapy in patients with breast cancer. J Clin Oncol 33:2262–2269CrossRef
35.
Mayer EL, Burstein HJ (2015) Adjuvant endocrine therapy for postmenopausal women: type and duration. Breast 24:S126–S128CrossRef
36.
Neugut AI, Hillyer GC, Kushi LH et al (2012) The breast cancer quality of care study (BQUAL): a multi-center study to determine causes for noncompliance with breast cancer adjuvant therapy. Breast J 18:203–213CrossRef
37.
Neugut AI, Zhong X, Wright JD et al (2016) Nonadherence to medications for chronic conditions and nonadherence to adjuvant hormonal therapy in women with breast cancer. JAMA Oncol 2(10):1326–1332CrossRef
38.
Hershman DL, Kushi LH, Hillyer GC et al (2016) Psychosocial factors related to non-persistence with adjuvant endocrine therapy among women with breast cancer: the breast cancer quality of care study (BQUAL). Breast Cancer Res Treat 157:133–143CrossRef
39.
Zwart W, Terra H, Linn SC et al (2015) Cognitive effects of endocrine therapy for breast cancer: keep calm and carry on? Nat Rev Clin Oncol 12:597–606CrossRef
40.
Ganz PA (2016) Understanding the impact of breast cancer adjuvant endocrine therapy on cognitive function: a work in progress. Br J Cancer 114:953–955CrossRef
41.
Daniel JM (2013) Estrogens, estrogen receptors, and female cognitive aging: the impact of timing. Horm Behav 63:231–237CrossRef
42.
Kesler SR, Kent JS, O’Hara R (2011) Prefrontal cortex and executive function impairments in primary breast cancer. Arch Neurol 68:1447–1453CrossRef
43.
Wefel JS, Vardy J, Ahles T et al (2011) International cognition and cancer task force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol 12:703–708CrossRef
44.
Hurria A, Patel SK, Mortimer J et al (2014) The effect of aromatase inhibition on the cognitive function of older patients with breast cancer. Clin Breast Cancer 14:132–140CrossRef
45.
Kool M, Fontein D, Kranenbarg EM et al (2015) Long term effects of extended adjuvant endocrine therapy on quality of life in breast cancer patients. Breast 24:224–229CrossRef
46.
Mandelblatt JS, Hurria A, McDonald BC et al (2013) Cognitive effects of cancer and its treatments at the intersection of aging: what do we know; what do we need to know? Semin Oncol 40:709–725CrossRef
47.
Mandelblatt JS, Jacobsen PB, Ahles T (2014) Cognitive effects of cancer systemic therapy: implications for the care of older patients and survivors. J Clin Oncol 32:2617–2626CrossRef
48.
Cohen HJ (2007) The cancer aging interface: a research agenda. J Clin Oncol 25:1945–1948CrossRef
49.
Cella D, Fallowfield LJ (2008) Recognition and management of treatment-related side effects for breast cancer patients receiving adjuvant endocrine therapy. Breast Cancer Res Treat 107:167–180CrossRef
50.
Fayers P, Aaronson N, Bjordal K et al (2015) The EORTC QLQ-C30 scoring manual. 2001. European Organisation for Research and Treatment of Cancer, Brussels, p 3
51.
Ercoli L, Petersen L, Hunter A et al (2015) Cognitive rehabilitation group intervention for breast cancer survivors: results of a randomized clinical trial. Psycho Oncol 24:1360–1367CrossRef
52.
Von Ah D, Carpenter JS, Saykin A et al (2012) Advanced cognitive training for breast cancer survivors: a randomized controlled trial. Breast Cancer Res Treat 135:799–809CrossRef
53.
Mustian KM, Sprod LK, Janelsins M et al (2012) Exercise recommendations for cancer-related fatigue, cognitive impairment, sleep problems, depression, pain, anxiety, and physical dysfunction: a review. Oncol Hematol Rev 8:81–88PubMedPubMedCentral
Metadata
Title
Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance)
Authors
Shirley M. Bluethmann
Catherine M. Alfano
Jonathan D. Clapp
George Luta
Brent J. Small
Arti Hurria
Harvey J. Cohen
Steven Sugarman
Hyman B. Muss
Claudine Isaacs
Jeanne S. Mandelblatt
Publication date
01-10-2017
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4353-y

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