Mandar S. Nadkarni

Single-Injection Depot Progesterone Before Surgery and Survival in Women With Operable Breast Cancer: A Randomized Controlled Trial

PURPOSE Many nonrandomized studies have suggested better outcome for patients with breast cancer who undergo surgery during the luteal (progestogenic) phase of their menstrual cycle, but this is controversial. We investigated the effect of a single preoperative injection of hydroxyprogesterone in women with operable breast cancer (OBC) in a randomized controlled trial (ClinicalTrials.gov identifier, NCT00123669). PATIENTS AND METHODS One thousand patients with OBC were randomly assigned to receive surgery or an intramuscular injection of depot hydroxyprogesterone 500 mg 5 to 14 days before surgery. Primary and secondary end points were disease-free survival (DFS) and overall survival (OS), respectively. An analysis by axillary lymph node status was preplanned. RESULTS At a median follow-up of 65 months among 976 eligible patients, 273 recurrences and 202 deaths were recorded. In the progesterone group versus control group, 5-year DFS and OS rates were 73.9% v 70.2% (hazard ratio [HR], 0.87; 95% CI, 0.68 to 1.09; P = .23) and 80.2% v 78.4% (HR, 0.92; 95% CI, 0.69 to 1.21; P = .53), respectively. In 471 node-positive patients, the 5-year DFS and OS rates in the progesterone group versus control group were 65.3% v 54.7% (HR, 0.72; 95% CI, 0.54 to 0.97; P = .02) and 75.7% v 66.8% (HR, 0.70; 95% CI, 0.49 to 0.99; P = .04), respectively. In multivariate analysis, DFS was significantly improved with progesterone in node-positive patients (adjusted HR, 0.71; 95% CI, 0.53 to 0.95; P = .02), whereas there was no significant effect in node-negative patients (P for interaction = .04). CONCLUSION A single injection of hydroxyprogesterone before surgery did not improve outcomes in all women with OBC. This intervention showed significant improvement in node-positive women that may be considered hypothesis generating. If replicated in other studies, this could be a simple and inexpensive intervention, especially in developing countries where the incidence of lymph node metastasis is high.

Hormone receptors over the last 8 years in a cancer referral center in India: what was and what is?

This study was carried out to observe the trend in hormone receptors over the last 8 years in a tertiary cancer center in India. A total of 11,780 tumors analyzed for hormone receptors over the last 7 years were compared with the results of hormone receptor expression in a prior published study on 798 cases of breast cancer from the same institute. The patients ages ranged from 18 to 102 years, Sixty percent of the patients were in the age group of 31-50 years. Seventy percent of the tumors were grade III tumors. The percentage of hormone receptor expression in breast cancer in the last 8 years varied from 52 to 57%. The overall receptor expression in the last 8 years shifted within a 5% range, confirming that the hormone receptor expression in Indian patients with breast cancer is low. However, there was redistribution within the pattern of estrogen receptor (ER) and progesterone receptor (PR) expression among tumors showing hormone receptor expression. Breast cancers showing only PR expression reduced dramatically from 21% in the year 1999 to in the year 2006, with a parallel increase in breast cancers showing combined ER and PR positivity (from 25 to 41.8%) and only ER expression (from 7.4 to 10.6%). The hormone receptor expression in breast cancers in India is and continues to be low but the high incidence of only PR-positive tumors in our population reported earlier was misrepresented.

INFLUENCE OF SURGICAL TECHNIQUE ON AXILLARY SEROMA FORMATION: A RANDOMIZED STUDY

The aim of this study was to evaluate the influence of surgical technique in the form of electrocautery and suction drains on seroma formation following surgery for breast cancer. A prospective randomized study was carried out. One hundred and sixty patients with breast cancer who underwent surgery were allocated to four arms using a 2 × 2 factorial design. This method enabled us to evaluate the independent effect of two different causative factors on the incidence of postoperative seroma formation using a single dataset with limited numbers. The main outcome measure was postoperative seroma formation defined as a postoperative axillary collection requiring more than one aspiration after removal of the drain. The incidence of seroma in our institution is 90%. Incidence of postoperative seroma was 88.3% if electrocautery was used, which reduced to 82.2% if surgery was carried out using scissors for dissection and ligatures for haemostasis (P = 0.358). There was no influence on the incidence of seroma formation whether suction drain (84.6%) or corrugated drains (86.1%) were used (P = 0.822). The use of electrocautery in axillary dissection does not adversely affect postoperative seroma formation after surgery for breast cancer. The use of different drainage techniques has no bearing on the postoperative seroma formation. The surgical technique has no influence on the rate of seroma formation after surgery for breast cancer.

Revision surgery for breast cancer: single-institution experience.

At Tata Memorial Hospital, as a dedicated breast service at a tertiary cancer center in India, incompletely performed breast surgeries are encountered very frequently; however, there is a lack of published data on incompletely performed breast surgeries, revision surgeries, and their outcomes. Between March 2000 and November 2003, the authors audited 850 breast cancer patients who presented at their institute who had undergone surgery outside the institution. On the basis of study criteria, these patients were evaluated for completeness of surgery. Patients in whom the surgical intervention was considered incomplete were evaluated for a completion revision surgery. Of 850 patients, 424 (50%) had undergone surgical intervention with therapeutic intent. Of these 424 patients, 191 (45%) had received incomplete surgical intervention. Completion revision surgery was performed for 153 patients. Complete data were available for 148 patients, of which 123 patients had residual lymph nodes in the axilla. The median number of lymph nodes dissected was 8, and 64 patients had metastatic lymph node(s) left behind. A high proportion of patients with breast cancer who presented at the institute had undergone incomplete surgery outside in nonspecialty centers. Almost half of those patients who underwent incomplete surgery had surgically excisable disease left behind. The possible detrimental impact of inadequate surgical intervention may be very large in India and in other low-resource settings. Cancer 2008;113(8 suppl):2347–52.

Feasibility of laparoscopic abdomino-perineal resection for large-sized anorectal cancers: a single-institution experience of 59 cases.

BACKGROUND Laparoscopic surgery for anorectal carcinoma is steadily gaining acceptance. While feasibility has already been reported, there are no reports addressing the impact of the actual size of large tumors on laparoscopic resectability. AIM To assess the feasibility and short-term results (including oncological surrogate end points) of performing laparoscopic abdomino-perineal resection (APR) for large rectal cancers. MATERIALS AND METHODS Data of 59 patients undergoing laparoscopic APR (LAPR) for anorectal malignancies were reviewed retrospectively. Outcomes were evaluated considering the surgical procedure, surface area of the tumor and short-term outcomes. RESULTS Of the 59 cases, LAPR could be completed in 53 (89.8%) patients. Thirty-one (58.4%) patients had Astler-Coller C2 stage disease. The mean surface area of the tumors was 24+/-17.5 (4-83) cm2. The number of median lymph nodes harvested per case was 12 (1-48). Circumferential resection margin (CRM) was positive in 11 (20.7%) patients. No mortality was reported. CONCLUSION This appears to be the first report analyzing the impact of the size of the rectal tumor in LAPR. The data clearly indicates that LAPR is not hampered by the size of the tumor. There appears to be a need for preoperative radiotherapy and chemotherapy before undertaking surgery on larger tumors in view of the higher circumferential resection margin positivity.

MEDIAL PECTORAL PEDICLE: A CRITICAL LANDMARK IN AXILLARY DISSECTION

Surgery for breast cancer has evolved over the last century and has gone from limited to radical, extended radical and back to conservative surgery. Along this journey, one constant feature has been the necessity for a complete axillary dissection. In recent times, this concept has also been successfully challenged and now we are in an era of conservative or limited surgery in the axilla as well. These surgical procedures such as four‐node axillary sampling or the technology‐driven sentinel node biopsy are conservative axillary procedures and are often performed through very small incisions. With limited access to the surgical field, there is always an increased chance of inadvertent and unnecessary injury to surrounding vital anatomical structures such as nerves or blood vessels. A well‐designed road map can definitely prevent such mishaps. This paper describes a simple technique of axillary surgery, which is step‐wise and makes use of a relatively constant landmark, namely the medial pectoral pedicle, present within the axilla. Such a regimented systematic approach not only allows us to minimize the risks of complications during axillary surgery, but also enables us to train beginners easily and efficiently.

Postoperative interstitial brachytherapy in eyelid cancer: long term results and assessment of Cosmesis After Interstitial Brachytherapy scale

Purpose To analyse feasibility and safety of postoperative interstitial brachytherapy (IBRT) in patients of eyelid cancer treated primarily by surgical excision. Material and methods In this series, 8 patients with eyelid cancer were treated using postoperative interstitial brachytherapy. Patients were followed up for local control, cosmetic outcome, and acute and late toxicities. Cosmetic outcome was measured using a 6 point indigenous Cosmesis After Interstitial Brachytherapy (CAIB) scale. Results The patients were between 23-82 years (median: 71 years). There were 3 females and 5 males, and 3 patients had lesions in upper eyelid. Postoperative high-dose-rate brachytherapy was used in all with 2 catheters implanted in most of them (6 out of 8). Local control was calculated from end of treatment to last follow-up. At last follow-up, all patients remained locally controlled. Two patients had nodal recurrence 6 months after interstitial brachytherapy and were salvaged effectively by external beam radiotherapy. At last follow-up, 7 patients were loco-regionally controlled and one was lost to follow up. All patients had Radiation Therapy Oncology Group (RTOG) grade 1 acute toxicity and 2 had grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version.3 late toxicities. The cosmesis score for the whole group ranged between 0-1 indicating excellent to very good cosmesis. Conclusions Postoperative high-dose-rate brachytherapy resulted in excellent disease control and cosmesis without significant acute or late toxicities. It is an effective modality for treatment of eyelid cancers in selected patients. Future prospective studies with the validation of CAIB scale would give us more insight to this effective yet often ignored modality of IBRT.

A Prospective Study of Computerized Digital Infrared Image Analysis (NoTouch BreastScanTM) in Biopsy Proven Breast Cancers.

Introduction: Early detection of breast cancer is known to have a more favourable outcome. Currently clinical breast examination and imaging modalities, primarily mammography are used for screening purposes. In India, more than 85% of the population is below the age of 50 years, wherein the sensitivity of mammography is at best 64%. Additional drawbacks of the procedure are physical discomfort and ionizing radiation dose to the patient. So newer techniques have been investigated which detect cancer induced neovascularity with digital thermal imaging. The purpose of this clinical study was to determine the efficacy of a software assisted thermal image analysis tool to distinguish between benign and malignant lesions of the breast.Methods: A prospective study was conducted in women who presented to the breast clinic with clinically or mammographically suspicious breast lesions. They also underwent thermal imaging of the breast. All mammographically suspicious lumps were subjected to histopathological confirmation. The mammography and infrared (IR) reports were compared to the histopathology.Results: In 90 women, 180 breasts were independently analyzed by both digital IR software analysis and mammography. Eighty five out of these 180 had suspicious lesions on mammography or clinical examination which were subjected to pathological confirmation. Mammography being the present diagnostic gold standard, all normal mammograms in clinically normal breast were considered as non-malignant. The sensitivity and specificity of digital thermography in detecting malignant lesions was 88.24% and 70.52% respectively with NPV of 87.01% and PPV of 72.82%. While for mammography the sensitivity and specificity were 96.25% and 96.7% with NPV of 96.7% and PPV of 96.25%. In women below 50 years of age (62/90) the sensitivity and specificity of digital thermography was 89.83% and 64.61% with NPV of 87.5% and PPV of 69.74%. Further, in the same subset no statistically significant difference was detected in the sensitivity of digital thermography to that of mammography (p = 0.7263).Conclusion: Our initial experience shows that the detection rate by digital thermal imaging is comparable to mammography in clinically palpable breast tumors. We also note that there is no significant difference in sensitivity of thermal imaging in women on either side of 50 making it a potentially testable tool for screening in younger women. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5028.

Single Injection Depot Progesterone Prior to Surgery and Survival in Women with Operable Breast Cancer: A Randomized Controlled Trial.

Background:The relationship between timing of surgery during menstrual cycle and survival in women with operable breast cancer (OBC) has been a subject of much debate. A meta-analysis of 37 retrospective studies revealed a modest survival benefit of 15%±8(2P=0.003) for those operated during progestogenic phase, whereas three prospective studies did not show any difference. Another meta-analysis of effect of circulating progesterone at the time of surgery showed a 53%±4(2P Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 72.

Does the patient's opinion differ from the clinicians' regarding breast cosmesis after BCT?

To the Editor: Women after breast conservation surgery have a better quality of life with respect to body image than following modified radical mastectomy, though eventually as time elapses, coping skills are known to equalize these differences (1–4). Eligibility for breast conservation treatment (BCT) is decided based on standard criteria including the clinician’s judgment of ‘‘good cosmesis’’ considering relative breast-tumor size ratio. The actual expectations and the final perception of the patient regarding her body image are really not clear at the time of such a decision. The appearance of breast is also known to change with gradual setting in of delayed fibrosis and eventual shrinkage in breast size as time elapses from surgery and after radiation therapy. This has a very important bearing on the overall quality of life over time after BCT. We carried out a prospective study to evaluate the differences in patients’ self-perception of level of satisfaction with their body image following BCT in comparison with the clinician’s appraisal of postconservation cosmesis over a period of time. The first assessment was made immediately after completion of adjuvant chemo-radiation therapy, followed up sequentially, at 6–12 monthly intervals follow-ups when the patient attended the breast clinic, until such time as she remained disease-free. A specially designed single-question questionnaire was served asking in simple terms to ‘‘grade their level of satisfaction with breast appearance and feel after breast conservation therapy’’. The observations were scored by the patient as four degrees of level of satisfaction namely ‘‘very happy’’ (VH), ‘‘satisfied’’ (S), ‘‘acceptable’’ (A), and ‘‘dissatisfied’’ (D). The clinicians’ opinion of cosmetic end result after BCT was noted independent of the patient’s observation and documented based on the JCRT criteria (5) scored as ‘‘excellent’’ indicating that the treated breast was identical to the untreated breast; ‘‘good’’ indicating treated breast was slightly different from the untreated breast; ‘‘fair’’, when the treated breast was clearly different from the untreated breast but not seriously distorted; and finally, ‘‘poor’’ indicating that the treated breast was seriously distorted. The comparative analysis was carried out with an a priori assumption that a ‘‘very happy’’ and ‘‘satisfied’’ mindset of the patient should correspond with an ‘‘excellent’’ and ‘‘good’’ cosmetic end-result as judged by the clinician. The Chi-squared test was applied to look for significance of the differences in observations by the patient and the clinician at various time intervals from surgery. A p-value of <0.05 was considered as statistically significant for all the tests. McNemar test was used to test for changes in response between two related observations in same individual at two different time points. All observations were broadly compared in three categories as follows: (a) the first or baseline observation by patient and clinician in all patients (at whichever time of presentation since surgery); (b) the subsequent observations at 6 monthly intervals since surgery and adjuvant therapy; (c) linear time scale observations were also compared in the same patient in subsequent yearly visits to note gradual changes in perception of cosmesis over time compared to first baseline observation made at 6 months from surgery. The questionnaires were completed and collected prospectively in women who had undergone their breast conservation surgery during January 2001 to May 2006. In all, 1,964 women participated in the patients’ self-assessment of body image and filled in 4,642 questionnaires at various time intervals. Similarly, in the clinicians’ appraisal of cosmesis, 1,759 patients were evaluated and 4,087 observations recorded. Both assessments (patient self-assessment and clinician’s appraisal) in the same patient was available in a subset of 652 patients at baseline (at completion of adjuvant therapy), 347 at visit 1 (after Address correspondence and reprint requests to: Dr. Vani Parmar, MS, DNB, Associate Professor, Division of Breast Services, Department of Surgical Oncology, Ernest Borges Road, Parel, Mumbai 400012, India, or e-mail: vaniparmar@gmail.com.