Described here is a single center, randomized controlled trial that recruited ninety-eight recently diagnosed women with stage II and III operable breast cancer who were awaiting breast cancer surgery. This study evaluated the effects of yoga intervention vs a supportive therapy with exercise rehabilitation in early stage II and III breast cancer patients undergoing breast cancer surgery. The selected women were recently diagnosed with breast cancer, with time following diagnosis ranging from 1 4 weeks. Subjects were recruited from January 2000 to June 2004 at a comprehensive cancer care center in Bangalore. The study was approved by the ethical committee of the recruiting cancer center. Patients were included if they met the following criteria: i) women with recently diagnosed operable breast cancer, ii) age between 30 to 70 years, iii) Zubrod s, performance status 0 2 (ambulatory > 50% of time), iv) high school education, iv) willingness to participate, v) Surgery as a primary treatment. Patients were excluded if they had i) a concurrent medical condition likely to interfere with the treatment, ii) any major psychiatric, neurological illness or autoimmune disorders, iii) secondary malignancy, iv) presented with infections or history of recent infections in the past month. The details of the study were explained to the participants and their informed consent was obtained.

Baseline assessments were done on 98 patients on the day prior to their surgery. Sixty-nine patients contributed data to the current analyses at the second assessment (four weeks after surgery). The reasons for dropouts were attributed to migration to other hospitals, use of other complementary therapies (e.g., Homeopathy or Ayurveda), lack of interest, time constraints and other concurrent illness.

Demographic information, medical history, clinical data, intake of medications and investigative notes were taken during their initial hospital visit before randomization. About 12 ml of blood sample was collected in vacuettes under sterile conditions on the day of the surgery. Blood samples were collected between 7 a.m. to 11 a.m. for all participants to reduce diurnal variability. Follow- up assessments were done at four weeks following surgery and before the commencement of any adjuvant treatment.

Subjects consenting to participate in this study were randomly allocated to receive either yoga (intervention) or supportive therapy plus exercise therapy prior to their surgery using random numbers generated by a random number table. Randomization was performed using opaque envelopes with group assignments, which were opened sequentially in the order of assignment during recruitment. These envelopes had names and registration numbers written on their covers. It was not possible to mask the yoga intervention from the subjects as yoga is a popular practice. However, the investigators (treating surgical oncologists) were blind to the intervention.

Breast cancer subjects in our study underwent surgery as a primary treatment. They underwent either breast conservation surgery (lumpectomy with axillary dissection) or (mastectomy with axillary dissection). We assessed the following postoperative outcomes: i) Number of days of drain retention following surgery  this is indicative of seroma collection at the wound site and is known to delay wound healing.[14] The criteria for drain removal followed in the hospital was drain fluid < 50 ml in 48 hours for all breast cancer surgery patients. ii) Duration of hospital stay (number of days in hospitalization)  patients were discharged if they were ambulatory, their general condition was good and did not have any postoperative complications. iii) Postoperative duration (interval between surgery and the start of any other adjuvant treatment). iv) Interval for suture removal (number of days from the day of surgery to the day of suture removal) the suture was removed when the approximated margins of the wound were closed (when primary union was facilitated). v) Presence of postoperative complications such as infections, secondary suturing, seroma, discharge, uncontrollable pain etc.

i)  Plasma levels of cytokines   TNF-alpha, IFN-gamma and soluble IL-2R alpha.

Quantifications of cytokines   sIL-2R, TNF-alpha and IFN-gamma: Two milliliters of blood samples were collected in sodium citrate vacuettes and plasma isolated for cytokine measurements.

Plasma was analyzed for cytokines using double sandwich ELISA techniques with Duoset ELISA Development kits from R & D Systems, USA. The test samples were run in duplicate and readings taken on a microplate reader (Organon Technica, USA). The test was calibrated using varying concentrations of a set of standards given along with the kit. The plates were read at 450 nm and standard curves plotted for each run with the log of cytokine concentrations on the y-axis and the log of the optical density (O.D.) readings on the x-axis; the best fit lines were determined by regression analyses. The concentrations were then extrapolated by using the mean O.D readings of the duplicate wells. The sensitivity of the tests was in the range of 15.7 998 15.8 950 and 31.5 2000 pg/ml for TNF-alpha, IFN-gamma and sIL-2 Ra  respectively.

The intervention group underwent an  integrated yoga program  and the control group received  supportive counseling and postoperative exercise rehabilitation.  While the goals of yoga intervention were stress reduction and improvement in shoulder mobility, the goals of the control intervention was to reinforce social support and prevent shoulder restriction. The yoga intervention consisted of a set of breathing exercises or Pranayama (voluntarily regulated nostril breathing) and yogic relaxation techniques. These practices were based on the principles of attention diversion and relaxation to cope with day-to-day stressful experiences.
Supportive counseling sessions as control intervention included two important components:  i) education and reinforcing social support and ii) shoulder exercise for postoperative rehabilitation . We used this as a control intervention mainly because it has been used earlier to hasten recovery from surgery  and to control for the nonspecific effects of the yoga program that may be associated with adjustment such as attention, support and a sense of control. Subjects and their caretakers were invited to participate in an introductory session lasting 60 minutes before surgery where they were given information about surgery and the management of its related side effects, taught shoulder exercises and mobilization by the physiotherapist and provided the answers to a variety of common questions. Both the interventions were imparted at the patient s bedside by trained personnel during the pre- and postoperative periods and subjects underwent four such in-person sessions in the hospital. Following their discharge, subjects were asked to practise their respective interventions at home daily (for half an hour) during the next three weeks. Subjects  interventions were monitored on a weekly basis by telephone calls. Subjects were also provided audiotapes of these practices for home practice using an instructor s voice so that a familiar voice could be heard on the cassette. Subjects were also encouraged to maintain a daily log listing the yoga practices done, use of audio-visual aids for practice, duration of practice, experience of distressful symptoms, intake of medication and diet history.

Data was analyzed using SPSS 10.0 for Windows. Data was tested for normality and homogeneity. An independent samples t test was done to assess postoperative outcomes between groups. The values of TNF-alpha were not normally distributed, hence, a nonparametric Mann Whitney U test was done on the change scores (pre- and postsurgery) to compare groups. A Chi Square test was done to analyze the difference in proportions among category variables across groups.
A multiple hierarchical regression analysis was done to examine the variance in dependent variables explained by independent variables. The dependent variables in this analysis were the number of days of drain retention, interval for suture removal, duration of hospital stay, postoperative duration (interval between surgery and adjuvant therapy). The independent prognostic variables entered into the analysis were age in years, type of surgery, size of tumor, postoperative surgery complications (presence or absence) and intervention. All models used the same set of five independent variables except for postsurgery TNF-alpha levels where a presurgery TNF- alpha level was added as an additional predictor. The ratio of subjects to the number of variables was 13.8 in the final model. For each equation, the probability of F-to-enter an independent variable was set at P < 0.10 and F- to-remove was set at P < 0.25. Probabilities were set at these levels so as to allow only for a small number of potential strong predictors to be selected in the models. The regression analysis was done using the entry method.