PR AMR falls and cancer treatment full article


Published on

Published in: Health & Medicine
  • Be the first to comment

  • Be the first to like this

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

PR AMR falls and cancer treatment full article

  1. 1. 1ORIGINAL ARTICLEIdentifying Factors Associated With Falls in PostmenopausalBreast Cancer Survivors: A Multi-Disciplinary ApproachKerri M. Winters-Stone, PhD, Britta Torgrimson, PhD, Fay Horak, PhD, PT, Alvin Eisner, PhD,Lillian Nail, PhD, RN, Michael C. Leo, PhD, Steve Chui, MD, Shiuh-Wen Luoh, MD 1,2 ABSTRACT. Winters-Stone KM, Torgrimson B, Horak F,Eisner A, Nail L, Leo MC, Chui S, Luoh S-W. Identifyingfactors associated with falls in postmenopausal breast cancer F because of theARE A PARTICULAR concern for and ad- RACTURES combined effect of chemotherapy BCS juvant endocrine therapy on fracture risk factors, includingsurvivors: a multi-disciplinary approach. Arch Phys Med Re- bone mass2 and fall risk.3 Even though falls may play anhabil 2011;xx:xxx. important role in fracture etiology,4 there are few studies of falls in BCS. We reported that BCS with chemotherapy- Objective: To identify neuromuscular, balance, and vision induced amenorrhea fall more than their age-matched, cancer-factors that contribute to falls in recently treated breast cancer free peers.5 Chen et al3 reported an increased number of falls insurvivors (BCS) and explore links between fall risk factors and BCS using data from the Women’s Health Initiative cohort.cancer treatment. In older adults, leading risk factors for falls include a prior Design: Case-control plus prospective observation. history of falls, muscle weakness, gait and/or balance impairment, Setting: Comprehensive cancer center. and poor vision.6-8 Cancer treatment may increase fall risk be- Participants: BCS (N 59; mean age, 58y) within 2 years of cause treatment can worsen traditional risk factors, potentiate lesschemotherapy completion and/or on adjuvant endocrine therapy. common risk factors, or contribute to falls in new ways. Breast Interventions: Not applicable. cancer chemotherapy may cause peripheral neuropathy9 and Main Outcome Measures: Objective measures of postural weakness.10 Adjuvant endocrine therapy has unknown effects oncontrol, vision, and neuromuscular function included: (1) a neuromuscular function and may alter vision in several ways.11-15sensory organization test (SOT), (2) a visual assessment bat- Despite study limitations that included examination of few falltery, (3) muscle mass by dual energy x-ray absorptiometry, and risk factors and use of simple balance and strength assessments,(4) neuromuscular function with strength by repetition maxi- our prior work suggests that both balance and strength are worsemum, power by timed stair climb, and gait speed by 4m walk. in estrogen-deficient BCS compared to controls and that falls areFalls were self-reported for the past year (retrospective) and more common in BCS with muscle weakness.5monthly for 6 months (prospective). The purpose of this study was to compare BCS with and Results: Fifty eight percent of BCS reported falls in the past without a recent history of falls on a comprehensive battery ofyear. BCS with a history of falls had lower SOT scores with a objective tests of fall risk factors. The objectives of this studyvestibular deficit pattern in postural control (P .01) and took were to: (1) identify balance, neuromuscular, and visual factorslonger to read letters on the contrast sensitivity chart (P .05). associated with past history of falls in BCS, (2) determine ifVestibular score on the SOT mediated the relationship between factors that discriminate past fallers from nonfallers can predicttreatment and falls among BCS who received chemotherapy future falls, and (3) examine whether balance, neuromuscular,only, but not adjuvant endocrine therapy. and visual factors are potential mediators of the relationship Conclusions: Results of this project suggest that balance between the type of cancer treatment and falls.disturbances of vestibular origin and delays in detecting lowcontrast visual stimuli are associated with falls in BCS. Future METHODSstudies that track falls and fall risk factors in BCS from diag-nosis through treatment are warranted, as are studies that can Sample and Settingidentify treatment-related vestibular dysfunction and alteredvisual processing. Women were recruited through state and hospital cancer Key Words: Drug therapy; Muscle strength; Neoplasms; registries, clinician referral, and community events. To bestPostural balance; Rehabilitation. evaluate persistent treatment effects rather than acute side © 2011 by the American Congress of Rehabilitation effects of cancer chemotherapy that might be linked to falls,Medicine eligibility criteria included a diagnosis of nonmetastatic breast cancer (stages 0 –IIIa), completion of chemotherapy within the past 2 years with or without adjuvant hormone therapy or within 2 years of surgery and presently taking a SERM or AI From the Schools of Nursing (Winters-Stone, Torgrimson, Leo, Nail), and Medi- that was initiated at least more than 6 months earlier, post-cine (Chui, Eisner, Horak, Luoh), Oregon Health and Science University; and the menopausal, and less than 70 years of age (to separate treat-Portland Veterans Affairs Medical Center (Luoh), Portland, OR. ment effects from aging). Women were excluded if they had This publication was made possible with support from the Oregon Clinical and cognitive difficulties or medical conditions that, in the opinionTranslational Research Institute (OCTRI), grant number UL1 RR024140 from theNational Center for Research Resources (NCRR), a component of the NationalInstitutes of Health (NIH), and NIH Roadmap for Medical Research. No commercial party having a direct financial interest in the results of the researchsupporting this article has or will confer a benefit on the authors or on any organi- List of Abbreviationszation with which the authors are associated. Reprint requests to Kerri M. Winters-Stone, PhD, Associate Professor, Oregon AI aromatase inhibitorHealth & Science University, 3455 SW US Veteran’s Hospital Rd, Mailcode: SN- BCS breast cancer survivorsORD, Portland, OR 97239, e-mail: SERM selective estrogen receptor modulator 0003-9993/11/xxx-00851$36.00/0 SOT sensory organization test doi:10.1016/j.apmr.2010.10.039 Arch Phys Med Rehabil Vol xx, Month 2011
  2. 2. 2 FALLS IN BREAST CANCER SURVIVORS, Winters-Stoneof the study investigator (K.W.S.), affected testing protocols. A conditions (fig 1) and provides equilibrium scores for eachconvenience sample size of 60 participants was targeted for this condition based on center of gravity sway. Sensory analysispreliminary study, balancing available resources, while retain- ratios are calculated to identify the degree to which a personing power for regression models. The institutional review can use information from the somatosensory, visual, and ves-board approved the study. tibular sensory systems to maintain balance, by comparing con- ditions 2 to 1, 4 to 1, and 5 to 1, respectively. The preference ratioProcedures determines reliance on visual information to maintain balance Women who responded to invitation letters from the can- even when the visual information is incorrect from sway-refer-cer registry, advertisements, or oncologist referral were con- encing the visual surround (conditions 3 vs 6 and 2 vs 5).tacted by telephone and screened for eligibility. Eligible Gait speed. Gait speed (m/s) was evaluated by timing thewomen who agreed to participate provided written informed participant as she walked in a straight line for 4m at bothconsent, completed questionnaires and underwent balance, normal and fast walking speeds on an electronic gait matneuromuscular, and vision testing. Tests were performed by (GAITrite electronic walkway systemb). Slow gait speed isthe same technician except for the SOT, which was admin- associated with increased fall risk.6istered by 1 of 2 trained physical therapists. All tests fol- Neuromuscular function. Neuromuscular function waslowed standard operating procedures that included moderate evaluated by the following tests: (1) maximal lower-bodyverbal encouragement. Participants also completed mailed strength by a 1-repetition maximum leg press (kg) (Vectra VXor e-mailed monthly fall reports for the next 6 months. Late 38 multi station weight machinec). using standard protocols18;reports ( 2 weeks) were followed up by phone and infor- (2) functional lower-body strength by length of time to rise 5mation was obtained verbally. times from a chair (s)19; and (3) functional stair climb ability, a task that relies on muscular power, by time to ascend andMeasures time to descend 7 stairs (1.2m) using standard protocols20 and Demographic and clinical characteristics. Demographic described as stair climb speed (m/s) and power (kg · m/s).and clinical characteristics including breast cancer stage, treat- Muscle mass. Muscle mass of the whole body was mea-ment type, diagnosis, and treatment dates were obtained by sured via dual energy x-ray absorptiometry (Hologic Discoveryself-report. Wi densitometerd). Participants lay supine on the table and Falls. Falls were assessed retrospectively through self-re- were positioned according to manufacturer guidelines for re-port of falls in the previous year and prospectively for 6 months gional body composition analysis.d Body composition wasby monthly reports. A fall was defined as unintentionally expressed as percent whole-body lean mass and leg lean masscoming to rest on the ground or at some other lower level, not (kg). In-house coefficients of variation for lean and fat mass inas a result of a major intrinsic event or overwhelming hazard.16 our laboratory are less than 2%.21A past fall was only counted if it occurred within the past year Vision characteristics. Vision characteristics were as-and after cancer diagnosis. To reduce reporting bias, we used a sessed with a visual function battery consisting of the followingstandard definition of a fall, gave identical instructions for tests: (1) visual acuity using autorefraction (Humphrey Autore-tracking falls to all participants regardless of fall history, and fractor/Keratometer Model 599e). (2) spatial contrast sensitiv-confirmed affirmative fall reports by telephone. ity (both eyes together) using the Pelli-Robson chart at a Balance problems. Balance problems consistent with neu- luminance level of 40cd/m2.22,f To assess task difficulty, weropathy, vestibular loss, and central nervous system disorders recorded Time to Hesitation as the time from the start of thethat contribute to fall risk17 were assessed by computerized test at highest contrast until subject first hesitated at 5 secondsdynamic posturography (Neurocom Clinical Research Sys- or longer between successive letters at lower contrasts. (3)tema). We conducted the SOT that systematically removes or Depth perception for near vision was assessed using the Randotalters useful visual and somatosensory input across 6 sensory SO-002 Graded Circle Stereoacuity Testg; (4) visual field sen- sitivity was measured using a white-on-white central 30° screening test (Humphrey Field Analyzer II model 750ie). Statistical Analysis Descriptive data for continuous variables are presented as means and SDs. Categorical data are presented as percentage of the sample. Independent samples t tests or chi-square were used for comparisons on balance, neuromuscular, vision, and treatment characteristics between BCS with and without a history of falls. To explore predictors of falls over and above a history of past falls, hierarchical logistic multiple regression was used to examine treatment, balance, neuromuscular, and vision variables that predicted fall status in the 6-month fol- low-up period with variables that differed between groups at P less than .15 considered for inclusion in the logistic regression model as independent variables. Treatment was dummy coded to examine the independent contributions of chemotherapy and adjuvant endocrine therapy to fall prediction. To examine whether balance, neuromuscular, and visual characteristics me- diate the relationship between treatment and falls, we em- ployed the product coefficients approach to testing media-Fig 1. Comparison of equilibrium scores by condition on the base-line SOT between BCS with a positive or negative fall history. tion.23-25 Only the variables that were significantly differentFigure illustrating the sensory system alterations are placed below between fallers and nonfallers at baseline were explored aseach condition number. mediators.Arch Phys Med Rehabil Vol xx, Month 2011
  3. 3. FALLS IN BREAST CANCER SURVIVORS, Winters-Stone 3 Table 1: Health History of Breast Cancer Survivors (N 59) Table 3: Comparison of Participants With Positive and Negative Fall History* on Demographic and Clinical Information Collected Mean SD or at Enrollment Treatment % of Sample Positive Fall Negative Fall Age (y) 58.5 9.7 History History BMI (kg/m2) 28.3 7.2 Characteristic (n 34) (n 25) P Months since diagnosis 20.9 6.5 Age (y) 59.2 7.1 57.4 12.4 0.52 Stage 0 5 Time since diagnosis (mo) 22.3 5.8 19.0 7.1 0.41 Stage I 29 Breast cancer stage 0.19 Stage II 39 Stage 0 9 0 N/A Stage III 19 Stage I 27 37 N/A Chemotherapy only (n 17) 29 Stage II 49 32 N/A Current adjuvant endocrine therapy (n 19) Stage III 15 31 N/A SERM use only (n 7) 12 Treatment Current AI use only (n 12) 20 Chemotherapy only 29 28 0.46 Chemotherapy and current SERM or AI Current SERM use only 15 4 0.28 use (n 23) 39 Current AI use only 15 24 0.16Abbreviation: BMI, body mass index. Chemotherapy and SERM or AI use 41 44 0.72 NOTE. Values are mean SD, % of group, or as otherwise noted. RESULTS Percentages reflect the proportion of the sample possessing a clin- ical characteristic within each fall group. *Number of falls reported over 12 months prior to baseline testing.Falls Of the 143 women who expressed interest in the study, 59women enrolled and all completed baseline testing and6-month fall reports. On average, participants were 58 years have a history of falls (P .05) (table 5). There were no otherold and overweight (table 1). Most women had stage I or II significant differences on the SOT, the muscle function tests, orbreast cancer, were treated with chemotherapy and were cur- the visual tests by fall history.rently taking a SERM or an AI. At enrollment, 58% reported a Predictors of Future Fallsfall in the previous year, and half experienced more than 1 fall(table 2). Less than 10% of the sample had a fracture after their After adjusting for fall history, the following variables werecancer diagnosis, but most reported fractures were associated added in the regression model: vestibular score, vision score,with a fall. Fifty-three percent of our sample experienced 1 or whole body percent lean mass, stair descent speed, time tomore falls during the 6-month follow-up period. One third of hesitation, and treatment type. Though stair ascent speed metwomen with a previous fall history also fell in the 6-month our criterion for entry in the model (P .15), it was not in-follow-up period. In this study, taking both observation periods cluded in the regression because of its large correlation withinto account, 76% of BCS reported falling after their cancer stair descent speed and concern for multicollinearity. Time todiagnosis within the 18-month time frame. (visual) hesitation and stair descent speed introduced instabilityDifferences Between Past Fallers and Nonfallers Past fallers and nonfallers were of similar age and clinical Table 4: Comparison of Participants With Positive and Negative Fall History* on Baseline Neuromuscular andstatus regarding breast cancer history (tables 3 and 4). Past Balance Characteristicsfallers had lower scores on condition 5 of the SOT (P .01)(see fig 1), which contributed to differences on the vestibular Positive Fall Negative Fall History Historyscore (P .01) (see table 4). Subjects who took longer time to Characteristic (n 34) (n 25) Pread letters on the contrast sensitivity chart were more likely to 2 BMI (kg/m ) 29.3 8.3 26.9 5.1 0.22 Whole body % lean mass 60.7 6.8 63.4 6.2 0.12 Table 2: Proportion of Falls and Fractures Reported by Leg lean mass (kg) 15.0 3.3 14.4 2.4 0.46 Breast Cancer Survivors (N 59) in the Past Year* and Maximal leg press (kg) 86.0 30.4 78.6 19.5 0.30 Over the 6-Month Observation Period Chair stand time (sec to Fall or Fracture Incidents % of Sample complete 5 stands) 12.6 3.0 11.8 3.3 0.31 Stair climb power At least 1 fall in past year 58 (kg · m/s) 28.3 6.7 28.2 7.0 0.96 Multiple falls in past year 31 Stair ascent speed (m/s) 0.25 0.04 0.27 0.05 0.09 Recent fracture 8 Stair descent speed (m/s) 0.28 0.07* 0.31 0.05 0.07 Recent fracture related to fall 5 Best fast walk (m/s) 0.43 0.07 0.48 0.07 0.21 At least 1 fall occurring over 6-month observation Average usual walk (m/s) 0.30 0.05 0.33 0.05 0.21 period 53 SOT-somatosensory 94.6 7.2 95.6 3.5 0.52 Multiple falls occurring over 6-month observation SOT-visual 77.6 19.1 84.1 8.5 0.12 period 14 SOT-vestibular 41.4 25.0 57.3 18.7 0.01 At least 1 fall in past year or over 6-month SOT-preference 96.6 23.6 98.6 11.5 0.70 observation period 76 NOTE. Values are mean SD or as otherwise noted.*Fall or fracture must have occurred within the year prior to enroll- Abbreviation: BMI, body mass index.ment and after cancer diagnosis. *Number of falls reported over 12 months prior to baseline testing. Arch Phys Med Rehabil Vol xx, Month 2011
  4. 4. 4 FALLS IN BREAST CANCER SURVIVORS, Winters-Stone Table 5: Comparison of Participants With Positive and Negative community-dwelling older adults over 65 years of age.26 In our Fall History* on Baseline Vision Characteristics study, 58% of BCS experienced a fall in the year prior to enroll- Positive Fall Negative Fall ment and nearly half (47%) fell within 6-months thereafter. Our History History results agree with those reported by Chen et al,3 that BCS have a Characteristic (n 34) (n 25) P 15% higher risk of falls than non-BCS. In contrast, studies in older Visual acuity – right eye† 0.9 0.2 0.9 0.3 0.63 cancer survivors report similar fall histories between older adults Visual acuity – left eye† 0.6 0.7 0.6 0.5 0.89 receiving treatment for cancer and cancer-free older adults.27,28 Contrast sensitivity‡ 1.8 0.2 1.8 0.2 0.73 Age and treatment differences may explain the discrepancies Contrast sensitivity time to between falls data in BCS studies versus studies of older adults hesitation (s)§ 29.0 10.5 24.6 6.1 0.04 with mixed cancer diagnoses. At least in BCS, higher fall risk Contrast sensitivity at should be considered as a potential consequence of treatment. In hesitation§ 1.7 0.1 1.7 0.1 0.99 turn, falls may lead to injury, activity limitations due to fear of Stereovision (arcsecond) 88.5 169.0 173.0 314.7 0.63 falling,29 and eventually contribute to functional decline.30 Visual field sensitivity (no. We measured a comprehensive set of neuromuscular and bal- of missed points)¶ 0.8 2.6 3.8 8.5 0.10 ance characteristics known to be associated with falls, but only balance discriminated fallers from nonfallers. BCS who fell hadNOTE. Values are mean SD or as otherwise noted. significantly lower scores on condition 5 of the SOT, indicating a*Number of falls reported over 12 months prior to baseline testing. vestibular-related deficit in balance control. Using similar meth-† Scores 1 indicate poorer than 20/20 acuity.‡ Higher scores indicate better contrast sensitivity. ods, Wampler et al31 reported lower scores on 5 of 6 SOT tests,§ Higher scores indicate more delay in detecting letters at low con- and particularly lower vestibular scores among BCS treated withtrast; sample sizes for contrast sensitivity were positive fall history: taxane therapy compared with healthy, age-matched controls.n 31 and negative fall history: n 23 and for contrast sensitivity SOT scores from our BCS group are similar to the BCS sample ofhesitation time and line were n 29 and n 22 due to missing data. Lower scores (arcsecond) indicate better stereovision. the Wampler31 study. However, in our study, the vestibular scores¶ Higher scores imply poorer coverage of the visual field. among the fallers are even lower and sway in other conditions was not abnormal. The similar SOT results for vestibular scores reported by both studies may reflect a consistent sidein the estimates of the SEs so the model was rerun without these effect of breast cancer treatment, particularly chemotherapy.variables. The final logistic regression model was not significant Doxobubicin (adriamycin), used in most combination chemo-( 26 3.85, P .05) (table 6). therapy for breast cancer, is an aminoglycoside. This class of drugs is associated with vestibular ototoxicity.32 Ototoxic sideMediators of the Relationship Between Treatment effects from chemotherapy drugs for breast cancer have re-and Falls ceived very little attention in the literature. Of the 2 studies Vestibular score was the only variable that met criteria for including BCS, aminoglycosides were linked to ototoxicity inmediator models. Separate models were run to examine BCS only,33 while ototoxicity from taxanes was not observedwhether vestibular score mediated the relationship between in breast plus ovarian cancer survivors.7 Ototoxicity results inpast or future falls and a particular treatment category (adjuvant loss of hair cells in the vestibular system even before noticeableendocrine therapy, chemotherapy, or adjuvant endocrine ther- hair cell loss in the cochlea for hearing and consistently re-apy and chemotherapy). Treatment type had an indirect rela- sults in abnormal scores in SOT conditions 5 and 6, despitetionship with past falls due to balance problems when relying normal sway in conditions 1 through 4.34 This study and theon the vestibular system (table 7). The chemotherapy only Wampler31 study suggest that breast cancer treatment maygroup was 1.96 times more likely to have a history of falls than adversely affect the vestibular inputs to balance control and thisthe group that received chemotherapy and endocrine therapy may lead to falls. However, because past, but not future falls,via the effect of treatment on vestibular score (95% bias- could be predicted by balance problems, it is possible thatcorrected and accelerated confidence interval for the odds vestibular or other deficits impairing balance function wereratio 1.05– 6.38). Vestibular score did not mediate the rela- most severe during and immediately following chemotherapytionship between treatment type and future falls. and lessen over time or are compensated for by increased reliance on other sensory systems to maintain balance.35 DISCUSSION Our study is the first to consider how breast cancer treatmentmay increase fall risk by using a comprehensive set of objec-tive measures of fall risk and by exploring mediators of the Table 6: Logistic Regression Results for Prediction of Faller Status Over 6-Month Observation Periodtreatment-falls relationship. Our findings suggest that recentlytreated postmenopausal BCS have higher rates of falling com- Independent Variable Odds Ratio (95% CI) Ppared with population averages for community-dwelling older History of falls in previous year 0.86 (0.27–2.69) 0.79adults. Balance disturbances may explain how treatment could Whole body percent lean mass 1.00 (0.92–1.01) 0.94increase falls in BCS. Difficulties responding quickly to low SOT-vision 0.97 (0.93–1.01) 0.17spatial contrasts may also contribute to falls in this population, SOT-vestibular 0.99 (0.97–1.03) 0.77in which vision disturbances associated with adjuvant endo- Adjuvant endocrine therapy only* 1.42 (0.41–4.90) 0.58crine therapy have been reported.11-15 By aggregating fall his- Chemotherapy only† 1.32 (0.31–5.64) 0.71tory data and prospective fall data, 76% of BCS fell within an18-month period. Alterations in vestibular inputs to balance NOTE. Independent variables were assessed at baseline.control may explain the relationship between breast cancer Abbreviation: CI, confidence interval.treatment and falls observed in women whose systemic treat- *Comparison of participants who only had adjuvant endocrine ther- apy to participants who had chemotherapy and adjuvant endocrinement was cytotoxic chemotherapy alone. therapy. Among our sample of postmenopausal BCS, the incidence of † Comparison of participants who had chemotherapy only compared tofalls is nearly double the 25% to 30% annual fall rate reported for participants who had chemotherapy and adjuvant endocrine therapy.Arch Phys Med Rehabil Vol xx, Month 2011
  5. 5. FALLS IN BREAST CANCER SURVIVORS, Winters-Stone 5 Table 7: Mediation Analysis to Test for the Indirect Effects of Treatment Type on Falls Via Vestibular Scores From the SOT 95% CI Pathway b SE P Odds Ratio* Odds Ratio Test of indirect path from adjuvant endocrine therapy only† as the independent variable Adjuvant endocrine therapy only to VEST score –6.43 6.84 0.35 N/A N/A Direct effects of VEST score on falls –0.04 0.01 0.02 0.96 0.94–0.98 Total effect of adjuvant endocrine therapy only on falls 0.47 0.61 0.45 1.60 0.48–5.29 Direct effect of adjuvant endocrine therapy only on falls 0.31 0.65 0.63 1.36 0.38–4.87 Partial effect of chemotherapy only on falls‡ –0.23 0.78 0.77 0.79 0.17–3.66 Indirect effects of adjuvant endocrine therapy only on falls through VEST score 0.22 0.30 N/A§ 1.25 0.76–2.64 Test of indirect path from chemotherapy only‡ as the independent variable Chemotherapy only to VEST score –19.41 7.72 0.02 N/A N/A Direct effects of VEST score on falls –0.04 0.01 0.02 0.96 0.94–0.98 Total effect of chemotherapy only on falls 0.40 0.69 0.57 1.49 0.39–5.77 Direct effect of chemotherapy only on falls –0.23 0.78 0.77 0.79 0.17–3.66 Partial effect of adjuvant endocrine therapy only on falls† 0.31 0.65 0.63 1.36 0.38–4.87 Indirect effects of chemotherapy only on falls through VEST score 0.68 0.49 N/A§ 1.96 1.05–6.38Abbreviations: CI, confidence interval; N/A, not applicable; VEST, vestibular.*Odds ratios reported only for logistic regression analyses.† Comparison of participants who only had adjuvant endocrine therapy to participants who had chemotherapy and adjuvant endocrine therapy.‡ Comparison of participants who had chemotherapy only compared to participants who had chemotherapy and adjuvant endocrine therapy.§ Normal theory tests are not available for models with binary outcomes. Confidence intervals are bias corrected and accelerated. Wampler et al also reported that BCS treated with taxane- effect; in fact, we only counted falls that occurred in the pastbased chemotherapy had worse visual acuity at low- but not year and after cancer diagnosis to retain the plausible link tohigh-contrast, as compared with healthy control subjects. In our cancer treatment. Due to challenges inherent to abstractingstudy, the average contrast sensitivity level itself was not medical records from diverse hospital systems among oursignificantly different between fallers and nonfallers, which community sample, we were unable to obtain full informationcould be because the Pelli-Robson test assesses contrast sen- on chemotherapy drugs and doses received by participants. Assitivity far above the visual acuity limit. In addition, we found a result, we cannot link specific chemotherapy agents to falls.the relation of falls to contrast sensitivity to depend on the time We did not include measures of peripheral neuropathy, a com-taken by subjects to respond correctly. In the absence of time mon side effect of chemotherapy associated with falls; how-constraints, subjects may view the low-contrast letters for up- ever, the SOT somatosensory scores were similar betweenwards of 10 seconds before identifying the correct letters. A fallers and nonfallers (see fig 1), suggesting that peripheraldecision period this long would be of little help to a personnavigating real-world environments where falls occur. Our neuropathy may not underlie balance problems in this sample.results may help explain discrepancies in the literature on the Our study may have attracted women concerned about fallingrelation of contrast sensitivity to falls.36-38 and results may not generalize to the broader population of In the mediator models, chemotherapy treatment had an BCS. Our sample size was relatively small but appropriate forindirect effect on falls through its effect on vestibular balance preliminary work and intended to inform future studies.scores when contrasted with the group that received chemo-therapy and adjuvant endocrine therapy where no relationship CONCLUSIONSwith vestibular balance scores and falls existed. However, therewas no indirect effect found for adjuvant endocrine therapy Falls in BCS are understudied and deserve more attention,only and falls via vestibular scores when compared to those particularly in light of the increase in fractures after breastwho received chemotherapy and adjuvant endocrine therapy. cancer treatment and the relationship of falls to fractures. OurThe differences between treatment groups may be confounded findings add to growing evidence that fall risk is increased inby different health and disease status of the patient that dictated BCS and that vestibular function may underpin associationstype of treatment. Women who do not receive adjuvant endo- between breast cancer treatment and falls. Our results alsocrine therapy for breast cancer are more likely to have hormone suggest that standard contrast sensitivity tests may not capturereceptor negative disease that is not responsive to SERMs or delays in contrast detection that might contribute to falls.AIs.39 These BCS may be more likely to receive high-dosechemotherapy40 and/or anthracycline-based chemotherapy41 Collectively, knowledge from this study will inform futurethus, may be more vulnerable to side effects of this type of studies of falls in cancer survivors as well as contribute to thechemotherapy treatment. Given the variation in dose and type development of specific interventions that target BCS at risk ofof chemotherapy and the impact of these variations on the falling. To date, only strength training has been examined fornature and magnitude of treatment-related side effects, it will effects on falls in BCS.42 This study did not specifically targetbe important for future studies to obtain complete treatment BCS who fell and exercise did not reduce falls. Given ourinformation on participants and/or focus on specific chemo- findings suggesting that strength is not a predictor of falls intherapeutic agents. BCS, strength training may be less effective in BCS than in older adults where strength is a predictor of falls. Future studiesStudy Limitations may consider multifactorial interventions for reducing falls that Our study has limitations. The analyses using retrospective include vestibular rehabilitation techniques and environmentalfalls data are cross-sectional and cannot establish cause and modifications to enhance contrast. Arch Phys Med Rehabil Vol xx, Month 2011
  6. 6. 6 FALLS IN BREAST CANCER SURVIVORS, Winters-Stone References 22. Rubin GS, West SK, Munoz B, Bandeen-Roche K, Zeger S, 1. Kanis JA, McCloskey EV, Powles T, Paterson AH, Ashley S, Schein O, Fried LP. A comprehensive assessment of visual im- Spector T. A high incidence of vertebral fracture in women with pairment in a population of older Americans. The SEE Study. breast cancer. Br J Cancer 1999;79:1179-81. Salisbury Eye Evaluation Project. Invest Ophthalmol Vis Sci 2. Howell A, Cuzick J, Baum M, et al. Results of the ATAC 1997;38:557-68. (Arimidex, Tamoxifen, Alone or in Combination) trial after com- 23. Hayes AF. Beyond Baron and Kenny: statistical mediation anal- pletion of 5 years’ adjuvant treatment for breast cancer. Lancet ysis in the new millennium. Communication Monographs 2009; 2005;365:60-2. 76:408-20. 3. Chen Z, Maricic M, Bassford TL, et al. Fracture risk among breast 24. MacKinnon DP, Lockwood CM, Williams J. Confidence limits for cancer survivors: results from the Women’s Health Initiative the indirect effect: distribution of the product and resampling Observational Study. Arch Int Med 2005;165:552-8. methods. Multivariate Behav Res 2004;39:99. 4. Frost HM. Should fracture risk-of-fracture analyses include an- 25. MacKinnon DP, Lockwood CM, Hoffman JM, West SG, Sheets other major risk factor? The case for falls. J Clin Densitom V. A comparison of methods to test mediation and other interven- 2001;4:381-3. 5. Winters-Stone KM, Nail L, Bennett JA, Schwartz A. Bone health ing variable effects. Psych Methods 2002;7:83-104. and falls: fracture risk in breast cancer survivors with chemother- 26. Hornbrook MC, Stevens VJ, Wingfield DJ, Hollis JF, Greenlick apy-induced amenorrhea. Oncol Nurs Forum 2009;36:315-25. MR, Ory MG. Preventing falls among community-dwelling older 6. Guideline for the prevention of falls in older persons. American persons: results from a randomized trial. Gerontologist 1994;34: Geriatrics Society, British Geriatrics Society, and American Acad- 16-23. emy of Orthopaedic Surgeons Panel on Falls Prevention. J Am 27. Overcash JA, Beckstead J. Predicting falls in older patients using Geriatr Soc 2001;49:664-72. components of a comprehensive geriatric assessment. Clin J On- 7. Sarafraz M, Ahmadi K. Paraclinical evaluation of side-effects of col Nurs 2008;12:941-9. taxanes on auditory system. Acta Otorhinolaryngol Ital 2008;28: 28. Overcash J. Prediction of falls in older adults with cancer: a 239-42. preliminary study. Oncol Nurs Forum 2007;34:341-6. 8. Dhital A, Pey T, Stanford MR. Visual loss and falls: a review. Eye 29. Salkeld G, Cameron I, Cumming R, et al. Quality of life related to (Lond) 2010;24:1437-46. fear of falling and hip fracture in older women: a time trade off 9. Kuroi K, Shimozuma K. Neurotoxicity of taxanes: symptoms and study. BMJ 2000;320:341-6. quality of life assessment. Breast Cancer 2004;11:92-9. 30. Deshpande N, Metter EJ, Lauretani F, Bandinelli S, Guralnik J,10. Mold JW, Vesely SK, Keyl BA, Schenk JB, Roberts M. The prev- Ferrucci L. Activity restriction induced by fear of falling and alence, predictors, and consequences of peripheral sensory neuropa- objective and subjective measures of physical function: a prospec- thy in older patients. J Am Board Fam Pract 2004;17:309-18. tive cohort study. J Am Geriatr Soc 2008;56:615-20.11. Eisner A, Austin DF, Samples JR. Short wavelength automated 31. Wampler MA, Topp KS, Miaskowski C, Byl NN, Rugo HS, perimetry and tamoxifen use. Br J Ophthalmol 2004;88:125-30. Hamel K. Quantitative and clinical description of postural insta-12. Epstein RJ. Visual impairment in myopic patients with breast bility in women with breast cancer treated with taxane chemo- cancer receiving adjuvant therapy with aromatase inhibitors. Clin Breast Cancer 2009;9:184-6. therapy. Arch Phys Med Rehab 2007;88:1002-8.13. Eisner A, Incognito LJ. The color appearance of stimuli detected 32. Black FO, Pesznecker SC. Vestibular ototoxicity. Clinical consid- via short-wavelength-sensitive cones for breast cancer survivors erations. Otolaryngol Clin North Am 1993;26:713-36. using tamoxifen. Vision Res 2006;46:1816-22. 33. Jenkins V, Beveridge H, Low R, Mitra S. Atypical hearing loss in14. Eisner A, Toomey MD, Falardeau J, Samples JR, Vetto JT. Differ- women with breast cancer receiving adjuvant treatment. Breast ential effects of tamoxifen and anastrozole on optic cup size in breast 2006;15:448-51. cancer survivors. Breast Cancer Res Treat 2007;106:161-70. 34. Black FO. What can posturography tell us about vestibular func-15. Coombes RC, Hall E, Gibson LJ, et al. A randomized trial of tion? Ann N Y Acad Sci 2001;942:446-64. exemestane after two to three years of tamoxifen therapy in 35. Horak FB. Postural compensation for vestibular loss and implica- postmenopausal women with primary breast cancer. New Engl tions for rehabilitation. Restor Neurol Neurosci 2010;28:57-68. J Med 2004;350:1081-92. 36. de Boer MR, Pluijm SM, Lips P, et al. Different aspects of visual16. Tinetti M, Williams C. Falls, injuries due to falls, and the risk of impairment as risk factors for falls and fractures in older men and admission to a nursing home. N Engl J Med 1997;337:1279-84. women. J Bone Min Res 2004;19:1539-47.17. Whitney SL, Marchetti GF, Schade AI. The relationship between 37. Lord SR. Visual risk factors for falls in older people. Age Ageing falls history and computerized dynamic posturography in persons 2006;(35 Suppl 2):ii42-ii45. with balance and vestibular disorders. Arch Phys Med Rehab 38. Freeman EE, Munoz B, Rubin G, West SK. Visual field loss 2006;87:402-7. increases the risk of falls in older adults: the Salisbury eye eval-18. American College of Sports Medicine. ACSM’s guildelines for uation. Invest Ophthalmol Vis Sci 2007;48:4445-50. exercise testing and prescription. 7th ed. Philadelphia: Lippincott 39. Chen JQ, Russo J. ERalpha-negative and triple negative breast Williams & Wilkins; 2006. cancer: molecular features and potential therapeutic approaches.19. Guralnik J, Simonsick E, Ferrucci L, et al. A short physical performance battery assessing lower extremity function: associa- Biochim Biophys Acta 2009;1796:162-75. tion with self-reported disability and prediction of mortality and 40. Nieto Y, Shpall EJ. High-dose chemotherapy for high-risk pri- nursing home admission. J Gerontol 1994;49:M85-94. mary and metastatic breast cancer: is another look warranted?20. Bean JF, Kiely DK, LaRose S, Alian J, Frontera WR. Is stair Curr Opin Oncol 2009;21:150-7. climb power a clinically relevant measure of leg power impair- 41. Berry DA, Cirrincione C, Henderson IC, et al. Estrogen-receptor ments in at-risk older adults? Arch Phys Med Rehab 2007;88: status and outcomes of modern chemotherapy for patients with 604-9. node-positive breast cancer. JAMA 2006;295:1658-67.21. Winters KM, Snow CM. Detraining reverses positive effects of 42. Twiss JJ, Waltman NL, Berg K, Ott CD, Gross GJ, Lindsey AM. exercise on the musculoskeletal system in premenopausal women. An exercise intervention for breast cancer survivors with bone J Bone Miner Res 2000;15:2495-503. loss. J Nurs Scholarsh 2009;41:20-7.Arch Phys Med Rehabil Vol xx, Month 2011
  7. 7. FALLS IN BREAST CANCER SURVIVORS, Winters-Stone 7 Suppliers e. Carl Zeiss Meditec Inc, 5160 Hacienda Dr, Dublin, CA 94568-a. NeuroCom International Inc, 9570 SE Lawnfield Rd, Clackamas, 7562. OR 97015. f. Lombart Instrument, 5358 Robin Hood Rd, Norfolk, Virginiab. CIR Systems Inc, 60 Garlor Dr, Havertown, PA 19083. 23513.c. Vectra Fitness, 7901 S 190th St, Kent, WA 98032. g. Stereo Optical Co, 8623 W Bryn Mawr Ave, Ste 502, Chicago, ILd. Hologic Inc, 35 Crosby Dr, Bedford, MA 01730. 60631. Arch Phys Med Rehabil Vol xx, Month 2011