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Keywords:

  • acupuncture;
  • aromatase inhibitor;
  • musculoskeletal symptoms;
  • patient-reported outcomes

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

BACKGROUND

Aromatase inhibitors (AIs) have been associated with decrements in patient-reported outcomes (PROs). The objective of this study was to assess whether real acupuncture (RA), compared with sham acupuncture (SA), improves PROs in patients with breast cancer who are receiving an adjuvant AI.

METHODS

Postmenopausal women with a stage 0 through III breast cancer who received an AI and had treatment-associated musculoskeletal symptoms were randomized to receive 8 weekly RA versus SA in a dual-center, randomized controlled trial. The National Surgical Adjuvant Breast and Bowel Project (NSABP) menopausal symptoms questionnaire, the Center for Epidemiological Studies Depression (CESD) scale, the Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index (PSQI), the hot flash daily diary, the Hot Flash-Related Daily Interference Scale (HFRDI), and the European quality-of-life survey (EuroQol) were used to assess PROs at baseline and at 4weeks, 8 weeks, and 12 weeks.

RESULTS

The intention-to-treat analysis included 23 patients in the RA arm and 24 patients in the SA arm. There were no significant differences in baseline characteristics between the 2 groups. Compared with baseline, scores in the RA arm improved significantly at week 8 on the CESD (P = .022), hot flash severity (P = .006), hot flash frequency (P = .011), the HFRDI (P = .014), and NSABP menopausal symptoms (P = .022); scores in the SA arm improved significantly on the EuroQol (P = .022),the HFRDI (P = .043), and NSABP menopausal symptoms (P = .005). Post-hoc analysis indicated that African American patients (n = 9) benefited more from RA than SA compared with non-African American patients (n = 38) in reducing hot flash severity (P < .001) and frequency (P < .001) scores.

CONCLUSIONS

Both RA and SA were associated with improvement in PROs among patients with breast cancer who were receiving AIs, and no significant difference was detected between arms. Racial differences in response to acupuncture warrant further study. Cancer 2014;120:381–389. © 2013 American Cancer Society.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Aromatase inhibitors (AIs) are the recommended primary adjuvant endocrine therapy for postmenopausal women with hormone-receptor-positive breast cancer.[1] AIs have been associated with worsening patient-reported outcomes (PROs), such as musculoskeletal symptoms and vasomotor symptoms.[2-6] One study demonstrated that 59% of women with early stage breast cancer who were receiving AIs experienced hot flashes, with 32% reporting moderate-to-severe hot flashes and 25% reporting significantly worsening hot flashes after the initiation of AI therapy.[6] The current treatments for AI-associated musculoskeletal and vasomotor symptoms are limited and may lead to drug discontinuation. Treatment for hot flashes include nonhormonal pharmacologic agents, such as clonidine, venlafaxine, gabapentin, and pregabalin; however, their use is limited because of suboptimal efficacy and potential side effects.[7, 8] Improved treatment of vasomotor symptoms in breast cancer patients is needed.

Acupuncture is a traditional Chinese medicine technique that involves inserting filiform stainless steel needles into specific points in the body to achieve therapeutic effect. Acupuncture reportedly alleviates vasomotor symptoms, decreases depression, and improves quality of life (QoL) in postmenopausal women, poststroke patients, and breast cancer survivors who are receiving tamoxifen.[9-12] To the best of our knowledge, no research has been conducted to study the effect of acupuncture in alleviating such symptoms in breast cancer survivors who receive AIs.

We previously conducted a dual-center, randomized, sham acupuncture (SA) (placebo)-controlled trial to assess the efficacy of real acupuncture (RA) in improving PROs in breast cancer patients who were receiving AIs. The primary endpoint of that study was the improvement of AI-associated musculoskeletal symptoms (AIMSS), and no statistically significant difference between the RA and SA arms was observed, although both groups reported improvement.[13] Prospective secondary endpoints included the effect of RA versus SA on other PROs that may be related to estrogen deprivation, such as menopausal symptoms, mood (depression, anxiety), sleep quality, and overall QoL, which are reported here.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Patients

Postmenopausal women with stage 0 through III hormone receptor-positive breast cancer who had been receiving AI therapy for ≥1 month, who reported AIMSS, and who had not received acupuncture within the past 12 months were included. Patients were treated at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center and the University of Maryland Greenebaum Cancer Center, and all provided informed consent before randomization. This clinical trial protocol was approved by the institutional review board of both institutes and is registered at clinicaltrials.gov (NCT00641303).

Interventions

Patients were randomized to an 8-weekly RA group or SA group. The randomization lists were generated by the trial statistician using specialized randomization software before the start of the trial. Randomization assignments were provided to the center acupuncturists. There were no deviations from the randomization lists. Although the randomization sequence was not concealed, the acupuncturists were not aware of the next assignment.

Although the acupuncturists were not blinded to the assignment, in an effort to minimize the introduction of bias, the acupuncturists followed a prepared script when engaging in conversation with the participants. All other individuals involved in the care of participants were blinded, including the treating oncologist(s), nurses, and study team members. The participants also were blinded to their treatment assignment.

Details of the RA and SA interventions have been reported previously.[13] Briefly, patients in the RA group received acupuncture in the conception vessel 4 (CV4), CV6, and CV12 points; the bilateral large intestine 4 (LI4) points; the Master of Heart 6 point (MH6); gall bladder point 34 (GB34); stomach point 36 (ST36); kidney point 3 (KI3); and urinary bladder point 65 (BL65). Patients in the SA group received nonpenetrating, retractable needles placed in 14 sham acupoints located at the midpoint of the line connecting 2 real acupoints.

Outcome Measures

We collected weekly hot flash diaries during weeks 0 through 8 and in week 12; and other PRO questionnaires were collected at baseline and at 4 weeks, 8 weeks, and 12 weeks. All questionnaires were in paper form, and the patients either completed the questionnaires in the clinic or completed them at home and returned them to the clinic during study visits. PROs that may have been related to estrogen deprivation, such as menopausal symptoms, mood (depression, anxiety), sleep quality, and overall QoL, were measured by using the PRO questionnaires described below: these instruments are commonly used among breast cancer survivors. In all but the European QoL (EuroQol) questionnaire, higher scores indicate worse symptoms.

Menopausal symptoms were assessed using the revised National Surgical Adjuvant Breast and Bowel Project (NSABP) menopausal symptoms questionnaire, which assesses 47 common symptoms. Respondents were asked to circle yes or no to indicate whether they had experienced the symptom during the previous week. If the menopausal symptom was present, then they were asked to rate its severity using a scale from 0 to 4. A total NSABP menopausal symptoms score was computed by summing items and ranged from 0 to 188. Reliability and validity have been previously reported.[14]

The Hot Flash-Related Daily Interference Scale (HFRDI) and the hot flash daily diary were used to assess the severity of hot flashes. The HFRDI is a 10-item scale measuring the degree to which hot flashes interfere with daily life activities, including work, social activities, leisure activities, sleep, mood, concentration, relations with others, sexuality, enjoyment of life, and overall QoL.[15] Participants rated the degree to which hot flashes had interfered with each item during the previous week using a scale from 0 (do not interfere) to 10 (completely interfere). A total score was computed by summing items and ranged from 0 to 100. Reliability and validity have been previously reported.[15]

The hot flash diary used in this trial was developed at the Mayo Clinic; it has been used in multiple double-blind, randomized studies of antihot flash agents, and it has been validated.[16] We have used these diaries in our pilot and in 2 randomized clinical trials of paroxetine for hot flashes.[17-19] If the symptom was present, then patients were then asked to rate the severity as 1 (mild), 2 (moderate), 3 (severe), or 4 (very severe). The hot flash weekly severity score was calculated as the sum of the product of the severity rating and the number of hot flashes.

Sleep quality and disturbance were assessed using the well validated Pittsburgh Sleep Quality Index (PSQI). The PSQI measures sleep quality and disturbance retrospectively over the previous month using self-reports.[20, 21] The PSQI consists of 18 items that produce a global sleep-quality score and the following 7 component scores: sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleeping medications, and daytime dysfunction. PSQI items use various response categories that include recording usual bed time, usual wake time, the number of actual hours slept, and the number of minutes to fall asleep as well as forced-choice Likert-type responses. Psychometric data suggest that the PSQI is a valid and reliable instrument to use in women with breast cancer.[21] A global PSQI score was computed by summing scores from the 7 component scores and ranged from 0 to 21. Reliability and validity have been previously reported.[21]

Depression or depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CESD). The CESD is a 20-item self-report measure that assesses the presence and severity of depressive symptoms occurring over the preceding week.[22] Respondents rate each item on a 4-point scale. After 4 positively worded items are reverse scored, responses are summed to obtain total scores, which range from 0 to 60. Scores of 16 and greater are indicative of high depressive symptoms. Psychometric properties of the CESD have been extensively examined, and the scale has been widely used in research, including our own breast cancer research.[23]

Anxiety was assessed with the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A). The HADS-A is a brief, 7-item scale that has been well validated as a measure of anxiety.[24] A total HADS-A score was computed by summing scores and ranged from 0 to 21.

An overall rating of QoL was assessed using the EuroQol. This is a Cantril-like ladder scale with 100 (best health) at the top and 0 (worst health [death]) at the bottom. Participants are asked to provide a single number to describe their own health state that day. They also are asked to provide a rating for the average woman their own age, for use as a comparison standard to judge their own rating. Reliability and validity have been previously reported.[25]

Statistical/Data Analysis

Statistical and data analyses of the secondary trial outcomes were predefined in the clinical protocol. Because the clinical trial sample size calculation was based on the primary outcomes, the analyses of secondary outcomes presented here should be considered hypothesis-generating. The intention-to-treat analysis included all patients who received at least 1 session of treatment and had at least 1 postbaseline efficacy assessment. For outcomes in which multiple repeated measures were made, the last-observation-carried-forward method was used to replace any missing values. Patients who missed baseline measurements for a PRO were excluded from the analysis for that PRO. The main comparison was differences between SA and RA in change from baseline to week 8 using a Wilcoxon signed-rank test. Change scores at week 8 were compared between groups with the Wilcoxon rank-sum test and with an analysis of covariance (ANCOVA), adjusting for baseline scores. Because the ANCOVA did not change the conclusions, it is the unadjusted analysis of change scores that is reported here. Post-hoc subgroup analyses were performed for each PRO on the intention-to-treat population based on 3 baseline characteristics: body mass index (BMI) (<30 kg/m2 or ≥30 kg/m2), age (<50 years or ≥50 years), and race (African American or non-African American), each of which was treated as a factor with 2 levels. An ordinary linear regression model was fitted to test the interaction between each baseline factor and treatment assignment after including both as main effects. Up to 2 statistically significant interaction tests (P < .05) would be expected by chance alone. All P values are 2-sided, and P < .05 was considered statistically significant. No adjustments for multiple comparisons were made.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Fifty-one patients were enrolled in the study and were randomized from May 2008 to July 2011. Four patients were excluded from the analysis, either because they did not initiate the intervention (n = 3) or they withdrew from the study early because of an issue unrelated to treatment (n = 1). The remaining 47 patients are included in this report. Twenty-three patients were randomized to receive RA, and 24 were randomized to receive SA (Fig. 1).The degree of missing data at each time point for each outcome is reported in the Consolidated Standards of Reporting Trials (CONSORT) diagram (see Fig. 1).

image

Figure 1. This is a Consolidated Standards of Reporting Trials (CONSORT) diagram of the current study. CESD indicates Center for Epidemiological Studies Depression scale; HADS, Hospital Anxiety and Depression Scale; Qol, the European quality-of-life (EuroQol) questionnaire; PSQI, Pittsburgh Sleep Quality Index; NSABP, National Surgical Adjuvant Breast and Bowel Project; HF, hot flash; HFRDI, Hot Flash-Related Daily Interference Scale.

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Baseline patient characteristics and PROs (NSABP, CESD, HADS, EuroQol, PSQI, hot flash weekly severity scores, hot flash weekly frequency, and HFRDI) were well balanced between the 2 groups (Tables 1 and 2). Among the 47 patients, baseline median weekly hot flash frequency was 13 (range, 0-73 weekly hot flashes). Eleven patients did not report hot flashes, 23 patients experienced hot flashes more than 14 times per week, and 13 experienced 1 to 13 hot flashes per week. Thirty patients had CESD scores <16, indicating that they were not likely to be depressed; 8 patients had CESD scores >16 and ≤20, indicating possible depression; and 9 patients had CESD scores >20, indicating probable depression. Forty-one patients had HADS scores ≥11, indicating possible anxiety. Among the 43 patients whose baseline PSQI scores were available, 41 had baseline PSQI scores >5, indicating poor sleep quality.

Table 1. Baseline Patient Clinical Characteristics and Patient-Reported Outcomes
 No. of Patients (%)
CharacteristicSham Acupuncture, N = 24Real Acupuncture, N = 23
  1. AI, aromatase inhibitor; BMI, body mass index.

Age: Median [range], y61 [44–82]61 [45–85]
Race  
Caucasian18 (75)16 (70)
African American5 (21)4 (17)
Other1 (4)3 (13)
BMI: Median [range], kg/m230 [23–46]32 [25–49]
Type of AI  
Letrozole9 (36)9 (39)
Anastrozole11 (45)8 (35)
Exemestane4 (17)6 (26)
Duration of AI: Median [range], d426 [137–1561]389 [109–1738]
Table 2. Summary of Patient-Reported Outcome Scores at Baseline, Week 4, Week 8, and Week 12 in the Real and Sham Acupuncture Arms
 SA ArmRA ArmPa
Assessment InstrumentMedianIQRMedianIQRIntergroupSA ArmRA Arm
  1. Abbreviations: CESD, Center for Epidemiological Studies Depression; EuroQoL, the European Quality of Life scale; HADS, Hospital Anxiety and Depression Scale; HFRDI, Hot Flash-Related Daily Interference Scale; IQR, interquartile range; NSABP, National Surgical Adjuvant Breast and Bowel Project; RA, real acupuncture; PSQI, Pittsburgh Sleep Quality Index; SA, sham acupuncture.

  2. a

    The last 3 columns of P values were from a between-group comparison (for change score at week 8 from baseline by Wilcoxon rank-sum test [Intergroup]) and within-group comparisons (between week 8 and baseline scores by Wilcoxon signed-rank test [SA arm and RA arm]).

CESD       
Baseline10.510169   
Wk 47.5151110.5   
Wk 8611.251010.5.442.099.022
Wk 127.511.751010.5   
HADS       
Baseline15.56144   
Wk 415.53.25144   
Wk 8163.25165.5.526.318.902
Wk 12155155.5   
EuroQoL       
Baseline80157520   
Wk 48512.57027.5   
Wk 88511.258027.5.146.022.833
Wk 1280208020   
PSQI       
Baseline92.7584   
Wk 47.55.7595   
Wk 89.5585.557.901.251
Wk 128.55.596   
Hot flash weekly severity score       
Baseline20.554.753167   
Wk 41967.752038   
Wk 81047.251432.5.467.602.006
Wk 121439.251438.5   
Hot flash weekly frequency       
Baseline15.5271332   
Wk 41029920   
Wk 8720.75815.5.487.328.011
Wk 12822.5821   
HFRDI       
Baseline8331129.5   
Wk 41022817   
Wk 8618.5413.5.633.043.014
Wk 12318.5812.5   
NSABP menopausal symptoms       
Baseline2529.252623   
Wk 420.525.252523   
Wk 819171818.5.463.005.022
Wk 121910.751727.5   

The median and interquartile range of each PRO score at baseline and at weeks 4, 8, and 12 are listed in Table 2. Between the 2 arms, there were no statistically significant differences in change scores on the PROs between baseline and week 8. Considering the SA and RA arms separately, there were statistically significant differences in change scores from baseline to week 8 for multiple PROs (P values listed in Table 2). Specifically, for the RA arm, the statistically significant mean ± standard deviation changes in scores from baseline to week 8 were as follows: CESD, −3 ± 6 (range, −14 to 10); hot flash severity score, −16 ± 26 (range, −74 to 29); hot flash frequency, −7 ± 11 (range, −32 to 15); HFRDI, −10 ± 18 (range, −52 to 19); and NSABP menopausal symptoms, −7 ± 14 (range, −33 to 15). For the SA arm, the statistically significant changes from baseline to week 8 were as follows: EuroQol, 6 ± 12 (range, −15 to 40); HFRDI, −9 ± 16 (range, −43 to 18); and NSABP menopausal symptoms, −9 ± 16 (range, −67 to 10).

Among the 36 patients who reported hot flashes at baseline, the median change in hot flash severity scores at week 8 was −11 (mean, −5; N = 18) for the SA group and −13.5 (mean, −20; N = 18) for the RA group. Among these patients, the median percentage change in hot flash severity scores from baseline was −54% (mean, 79%; N = 18) for the SA group and −31% (mean, − 37%; N = 18) for the RA group.

In each subgroup analysis for the week 8 change score, the interaction term between the baseline factor (BMI, age, or race) and the treatment assignment was tested. A significant test of interaction was an indication of effect modification by the baseline factor. In the multiple post-hoc subgroup analyses performed, 4 tests of interaction were significant: hot flash weekly severity score (P < .001), hot flash weekly frequency (P < .001), and HFRDI (P = .048) with respect to race (all with AA patients benefitting more from RA), and EuroQol (P = .044) with respect to age (patients aged <50 years benefitted more from RA). For the hot flash weekly severity score and hot flash weekly frequency, the treatment effect estimates and 95% confidence intervals for each subgroup are presented in Figure 2. The treatment effect is defined as the difference in the week 8 change score between the 2 groups (RA vs SA). For both PROs, AA patients benefitted significantly more from RA than non-AA patients. The 95% confidence intervals of AA patients also differed significantly from the overall treatment-effect point and the no-effect point. During the study, 3 non-AA patients reported taking venlafaxine for hot flashes, whereas none of the AA patients reported taking venlafaxine. This racial difference may be because of both a worse response of AA patients to SA and a better response to RA compared with non-AA patients (Fig. 3A,B).

image

Figure 2. These forest plots for subgroup analysis were based on body mass index (BMI) (≥30 kg/m2 vs <30 kg/m2), age (≥50 years vs <50 years), and race (African American [AA] vs non-AA) and display treatment effects across subgroups for (A) the hot flash (HF) weekly severity score and (B) HF weekly frequency. A dashed vertical line indicates the point of no effect, and a solid vertical line indicates the point of overall treatment effect. In the sham acupuncture (SA) arm, there were 5 AA patients versus 19 non-AA patients, 21 patients aged ≥50 years versus 3 patients aged <50 years, and 11 patients with a BMI ≥30 kg/m2 versus 7 patients with a BMI <30 kg/m2. In the real acupuncture (RA) arm, there were 4 AA patients versus 19 non-AA patients, 20 patients aged ≥50 years versus 3 patients aged <50 years, and 14 patients with a BMI ≥30 kg/m2 versus 8 patients with a BMI <30 kg/m2. CI indicates confidence interval.

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image

Figure 3. This interaction plot illustrates different racial responses to real acupuncture (RA) versus sham acupuncture (SA) according to the hot flash (HF) weekly severity score. AA indicates African American.

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DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Our study demonstrated that some PROs, such as hot flashes, improved significantly after RA or SA treatments in patients with early stage breast cancer who were receiving AIs, although there was no significant difference between the 2 groups. A post-hoc subgroup analysis indicated more treatment benefit for AA patients than non-AA patients with regard to hot flash frequency, hot flash severity, and HFRDI scores, which was because of both a worse response for AA patients to SA and a better response for them to RA compared with non-AA patients.

To date, 4 systematic reports of QoL data from the major AI adjuvant trials using validated QoL instruments have been published. In the Anastrozole, Tamoxifen, or the Combination (ATAC) trial (N = 1021), overall QoL improved over time in all treatment groups, with no significant difference observed between groups. Endocrine-related symptoms, such as vasomotor complaints and sexual dysfunction, however, worsened at the initiation of AI therapy, and then partially recovered.[3] In the Intergroup Exemestane Study (IES) QoL substudy (N = 482), no significant changes in overall QoL were observed, although vasomotor symptoms improved over time in both treatment groups (tamoxifen vs tamoxifen followed by exemestane).[4] The MA.17 QoL substudy (N = 3612) reported no significant intergroup difference in overall QoL, but statistically significant worsening body pain and vasomotor symptoms were reported in patients who were randomized to the letrozole group.[5] Finally, the Tamoxifen Exemestane Adjuvant Multinational (TEAM) Trial QoL substudy (N = 742) reported that, over the 1 year between years 1 and 2 while receiving hormone treatment, there were no relevant differences in QoL between the 2 groups; although, over time, most functional QoL scores improved with the exception of physical and sexual function.[26]

Few acupuncture clinical trials have focused on studying hot flashes in women who are receiving AIs. Our results are consistent with the majority of the existing acupuncture literature on the benefit of the approach to treating hot flashes, demonstrating that patients benefit from both RA and SA, with no significant difference between groups.[11, 27] Those studies raise the question of whether SA is truly inert or may induce physiological effects similar to those produced by RA. The lack of between-group differences may also be explained by the small sample size of the current study. The primary endpoint of this study was the improvement of AIMSS, and it was not powered to detect statistically significant differences between RA and SA in improving PROs like hot flashes. The acupuncture points used in this study were designed to treat AIMSS; however, approximately 60% of the acupuncture points overlap with those used in treating hot flashes, which may explain the significant improvement in hot flashes in the RA arm.

Our study demonstrated a mean reduction in the percentage hot flash severity score of 37% in the RA arm. This reduction is greater than the 20% hot flash reduction observed with clonidine[28] but is less than reductions reported with antidepressants like paroxetine (45.6% reduction),[19] fluoxetine (50% reduction),[29] and venlafaxine (60% reduction).[30] However, acupuncture treatment was not associated with any significant side effects, whereas clonidine and antidepressants were associated with multiple side effects, including mouth dryness, nausea, constipation, and drowsiness.[19, 28-30] It is noteworthy that the median percentage reduction in the hot flash severity score for the SA arm was 54%, although the mean percentage hot flash severity score increased by 79% because of 3 outlier patients who had significantly worsened hot flash severity scores during the study. A study with a larger sample size is needed to determine whether RA is significantly more effective than SA.

There have been major controversies regarding the use of SA in designing clinical trials.[31] Although many researchers believe that acupuncture studies should include a placebo control arm, prospective experiences have demonstrated extreme difficulties identifying a truly inert SA control. It has been demonstrated that minimal acupuncture with needles inserted only 1 or 2 mm below the skin stimulates cutaneous afferent nerves and evokes an analgesic effect.[32] Procedures with noninsertion of the needle are likely to produce similar effects. Systematic reviews have revealed no significant differences in outcome when stimulating acupuncture points or nonacupuncture points.[33, 34] In our study, we used both nonpenetrating needles and nonacupuncture points as SA, which still significantly improved some patients' PROs, suggesting that our sham control may not be inert and may have underlying physiologic effects.

To the best of our knowledge, our study is the first to explore the possible racial differences in response to RA versus SA. The etiology of such a racial difference is not clear and should be explored further based on our intriguing results. Although, historically, AA women have tended to report more severe and more frequent hot flashes,[35] this was not the case in our study. In our patients, the baseline hot flash severity and frequency were balanced between AA patients and non-AA patients. This racial difference cannot be explained by the use of antihot flash medication, because more non-AA patients than AA patients received antihot flash medication during the study. The reason why AA patients had a worse response to SA than non-AA patients remains unclear and warrants further study. Because only a few AA patients (N = 9) were enrolled in this trial, no definitive conclusion can be drawn, and our results must be regarded as hypothesis-generating. Further study involving a larger number of AA patients will help produce a better estimate of the treatment effect of RA in AA patients.

Our study was limited by its small sample size, which was not powered to detect differences between RA and SA, and by the lack of a usual care group to determine whether SA is an active intervention beyond regression to the mean. Our trial demonstrated that, in patients with early stage breast cancer who were receiving AIs, some PROS, especially hot flashes, improved significantly after 8-weekly RA or SA, although there was no significant difference between responses to the 2 interventions. Failure to observe between-group differences may have been because of the small sample size of the trial and because SA may not be inert. It is noteworthy that no significant side effects were associated with either intervention. Further studies with larger sample sizes are required to definitively evaluate the benefit of acupuncture.

FUNDING SUPPORT

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

This trial was supported by an American Society of Clinical Oncology Foundation Young Investigator's Award, a Susan Komen Postdoctoral Fellowship Award, the Breast Cancer Research Foundation, and a Craft grant from the Maryland Affiliate of Susan G. Komen for the Cure. Ting Bao is a Paul Calabresi scholar (grant K12 CA126849) and is supported by R21 CA173263. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins receives funding from the National Cancer Institute (grant P30 CA006973). The University of Maryland Greenebaum Cancer Center also receives funding from the National Cancer Institute (grant P30 CA134274).

CONFLICT OF INTEREST DISCLOSURES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Saranya Chumsri has received compensation as a consultant from Novartis and receives research funding from Novartis, GSK, and Merck. Vered Stearns receives research funding from Pfizer and Novartis.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES
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  • 2
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  • 3
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  • 4
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