S1200: Acupuncture, Sham Acupuncture, or Wait List for Joint Symptoms Related to Aromatase Inhibitors in Pts W/Early-Stage Breast Cancer

OBJECTIVES:

Primary

- To determine whether true acupuncture administered twice weekly for 6 weeks (8-12
sessions) compared to sham acupuncture and waitlist control causes a significant
reduction in joint pain related to aromatase inhibitors (AIs) in women with early-stage
breast cancer as measured by the Brief Pain Inventory-Short Form (BPI-SF) worst pain
score at 6 weeks.

Secondary

- To investigate the effects of true acupuncture administered twice weekly for 6 weeks
(8-12 sessions) followed by 6 weekly treatments (4-6 sessions) of maintenance (12-18
sessions total over 12 weeks) compared to sham acupuncture and waitlist control in this
study population; the evaluations at 12 and 24 weeks are to determine the benefit of
additional 6 weekly acupuncture treatments for maintenance and to determine the
durability of response after stopping acupuncture, respectively; the evaluation at 52
weeks is to determine the long-term effects of acupuncture and adherence to AIs.

- To evaluate the effects of acupuncture on the BPI-SF worst pain, worst stiffness, pain
severity, and pain-related interference scores at 6, 12, 16, 20, 24, and 52 weeks.

- To evaluate the effects of acupuncture on Western Ontario and McMaster Universities
Osteoarthritis (WOMAC) index (pain, stiffness, and function) for the hips and knees at
6, 12, 24, and 52 weeks.

- To evaluate the effects of acupuncture on Modified-Score for the Assessment and
Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH) (pain,
stiffness, and function) at 6, 12, 24, and 52 weeks.

- To evaluate the effects of acupuncture on the PROMIS Pain Impact-Short Form (PROMIS
PI-SF) at 6, 12, 24, and 52 weeks.

- To evaluate the effects of acupuncture on quality of life (QOL) as assessed by the
Functional Assessment of Cancer Therapy-Endocrine Subscales (FACT-ES) at 6, 12, 24, and
52 weeks.

- To evaluate the effects of acupuncture on functional testing with grip strength and
"Timed Get Up and Go" (TGUG) test at 6, 12, 24, and 52 weeks.

- To evaluate the effects of acupuncture on analgesic and opioid use at 2, 4, 6, 12, 16,
20, 24, and 52 weeks.

- To evaluate the effects of acupuncture on self-reported AI adherence at 12, 24, and 52
weeks.

- To assess AI adherence via urine AI metabolites at baseline, 24, and 52 weeks.

- To evaluate the effects of acupuncture on serum hormones (estradiol, FSH, LH) and
inflammatory biomarkers (serum TNFα, IL-6, IL-12, CRP, and urine c-telopeptides of Type
II collagen (CTX-II) at 6, 12, and 24 weeks. (Exploratory)

- To evaluate whether polymorphisms in CYP19A1 aromatase gene predict severity of
AI-related joint symptoms. (Exploratory)

- To assess the safety and tolerability of acupuncture in this study population.

OUTLINE: This is a multicenter study. Patients are stratified according to study site.
Patients are randomized to 1 of 3 treatment arms.

- Arm I: Patients receive acupuncture twice weekly for 6 weeks and then once weekly for 6
weeks.

- Arm II: Patients receive sham acupuncture twice weekly for 6 weeks and then once weekly
for 6 weeks.

- Arm III: Patients are assigned to a waiting list for 12 weeks. Patients complete the
Brief Pain Inventory-Short Form (BPI-SF), the Western Ontario and McMaster Universities
Osteoarthritis (WOMAC) Index, the Modified-Score for the Assessment and Quantification
of Chronic Rheumatoid Affections of the Hands (M-SACRAH), the PROMIS Pain Impact-Short
Form (PROMIS PI-SF), the FACT-ES Trial Outcome Index, and the Aromatase Inhibitor Usage
Form questionnaires at baseline and at 6, 12, 24 and 52 weeks.

Patients undergo blood sample collection at baseline and at 6, 12, and 24 weeks for serum
hormones (estradiol, FSH, LH) levels, inflammatory markers (TNFα, IL-6, IL-12, CRP), and DNA
analysis. Urine samples are also collected at baseline and at 24 and 52 weeks for
c-telopeptides of Type II collagen and aromatase inhibitor metabolites analysis.

After completion of study treatment, patients are followed up at 24 and 52 weeks.

DISEASE CHARACTERISTICS:

- Patients must be women with histologically confirmed primary invasive carcinoma of the
breast (Stage I, II, or III) with no evidence of metastatic disease (M0); patients
must have undergone modified radical mastectomy or breast-sparing surgery; patients
must have recovered from all side-effects of the surgery

- Patients must be positive for estrogen receptor (ER) and/or progesterone receptor
(PgR) as determined by institutional standard

- Patients must currently be taking a third-generation aromatase inhibitor (AI) -
anastrozole, letrozole, or exemestane for at least the previous 90 days prior to
registration with plans to continue for at least an additional 1 year after
registration; patients may have switched AIs provided that they have been on a stable
dose for at least 90 days; concurrent trastuzumab (Herceptin) is allowed

- Patients must have completed the S1200 Brief Pain Inventory-Short Form (BPI-SF) within
14 days prior to registration; patients must have a worst pain score of at least 3 on
the Brief Pain Inventory (item #2) that has started or increased since starting AI
therapy

- Patients must be willing to submit blood and urine samples for serum hormones
(estradiol, FSH, LH), inflammatory biomarkers (serum TNFα, IL-6, IL-12, CRP and urine
CTX-II), urine AI metabolites, and DNA analysis (CYP19A1), and must be given the
option to consent to use of remaining specimens for future translational medicine
studies; baseline samples must be obtained prior to beginning intervention

PATIENT CHARACTERISTICS:

- Patients must be postmenopausal, as defined by at least one of the following:

- ≥ 12 months since the last menstrual period

- Prior bilateral oophorectomy

- Current use of a gonadotropin-releasing hormone (GnRH) agonist

- Previous hysterectomy with one or both ovaries left in place (or previous
hysterectomy in which documentation of bilateral oophorectomy is unavailable) AND
follicle-stimulating hormone (FSH) values consistent with the institutional
normal values for the postmenopausal state; if patient is under the age of 55,
FSH levels must be obtained within 28 days prior to registration

- Patients must have a Zubrod performance status of 0 to 1

- Patients must not have a severe bleeding disorder

- Patients must not have concurrent medical/arthritic disease that could confound or
interfere with evaluation of pain or efficacy including: inflammatory arthritis (e.g.,
rheumatoid arthritis, systemic lupus, spondyloarthropathy, psoriatic arthritis,
polymyalgia rheumatica), gout, episodes of acute monoarticular arthritis clinically
consistent with pseudogout, Paget disease affecting the study joint (knees/hands), a
history of septic arthritis or avascular necrosis or intra-articular fracture of the
study joint, Wilson disease, hemochromatosis, alkaptonuria, or primary
osteochondromatosis

- Patients must not have a history of bone fracture or surgery of the afflicted knees
and/or hands within 6 months prior to registration

- Patients must not have a history of illness that, in the opinion of the investigator,
might confound the results of the study or pose additional risk to the patient

- Patients must be able to complete study questionnaires in English or Spanish

- No other prior malignancy is allowed except for adequately treated basal cell or
squamous cell skin cancer, in situ cervical cancer, ductal carcinoma in situ [DCIS],
adequately treated Stage I or II cancer from which the patient is currently in
complete remission, or any other cancer for which the patient has been disease-free
for > 5 years

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Patients must not have had prior acupuncture treatment within the past 12 months or
for AI-induced joint symptoms at any time

- Patients must not be on narcotics within 14 days of registration

- Patients must not have received oral corticosteroids, intramuscular corticosteroids,
or intra-articular steroids within 28 days prior to registration

- Patients must not have received topical analgesics (e.g., capsaicin preparations) or
any other analgesics (e.g., opiates or tramadol, with the exception of nonsteroidal
anti-inflammatory drugs [NSAIDs] and acetaminophen) within 14 days prior to
registration

- Patients must not have received or implemented any other medical therapy, alternative
therapy, or physical therapy for the treatment of joint pain/stiffness within 28 days
prior to registration; therapeutic massage is allowed