Krishna B. Clough

Improving breast cancer surgery: a classification and quadrant per quadrant atlas for oncoplastic surgery.

BackgroundOncoplastic surgery (OPS) has emerged as a new approach for extending breast conserving surgery (BCS) possibilities, reducing both mastectomy and re-excision rates, while avoiding breast deformities. OPS is based upon the integration of plastic surgery techniques for immediate reshaping after wide excision for breast cancer. A simple guide for choosing the appropriate OPS procedure is not available.ObjectiveTo develop an Atlas and guideline for oncoplastic surgery (OPS) to help in patient selection and choice of optimal surgical procedure for breast cancer patients undergoing BCS.MethodsWe stratify OPS into two levels based on excision volume and the complexity of the reshaping technique. For resections less than 20% of the breast volume (level I OPS), a step-by-step approach allows easy reshaping of the breast. For larger resections (level II OPS), a mammoplasty technique is required.ResultsWe identified three elements that can be used for patient selection and for determination of the appropriate OPS technique: excision volume, tumor location, and glandular density. For level II techniques, we defined a quadrant per quadrant Atlas that offers a different mammoplasty for each quadrant of the breast.ConclusionsOPS is the “third pathway” between standard BCS and mastectomy. The OPS classification and Atlas improves patient selection and allows a uniform approach for surgeons. It proposes a specific solution for different scenarios and helps improve breast conservation outcomes.

prospective Evaluation of Late Cosmetic Results following Breast Reconstruction: I. Implant Reconstruction

The long‐term cosmetic outcome of breast implant reconstruction is unknown. The morbidity and cosmetic outcome of 360 patients who underwent immediate postmastectomy breast reconstruction with various types of implants have been analyzed prospectively over a 9‐year period. Of these patients, 334 who completed their reconstruction were suitable for evaluation of their cosmetic outcome. The early complication rate (< 2 months) was 9.2 percent, with an explantation rate of 1.7 percent. The late complication rate (> 2 months) was 23 percent, with a pathological capsular contracture rate of 11 percent at 2 years and 15 percent at 5 years and an implant removal rate of 7 percent. The revisional surgery rate was 30.2 percent. The cosmetic results were assessed prospectively using an objective five‐point global scale. Every patient was scored at each visit once surgery was completed. The overall cosmetic outcome deteriorated in a linear fashion, from an initial acceptable result of 86 percent 2 years after patients completed their reconstruction to only 54 percent at 5 years. This decline in cosmetic outcome was not associated with the type of implant used, the volume of the implant, the age of the patient, or the type of mastectomy incision employed. Radiotherapy was not a significant factor because only 28 patients were irradiated. Upon Cox model analysis, pathological capsular contracture was the only factor that contributed significantly to a poor cosmetic outcome in which p < 0.0001 (relative risk 6.3). Despite a high revisional surgery rate, deterioration still occurred, suggesting that other unaccounted for variables were responsible. On photographic retrospective review of the patients without capsular contracture who demonstrated deterioration in their cosmetic scores, it became clear that a possible reason for their poor results was late asymmetry produced by the failure of both breasts to undergo symmetrical ptosis with aging. (Plast. Reconstr. Surg. 107: 1702, 2001.)

Axillary Treatment in Conservative Management of Operable Breast Cancer: Dissection or Radiotherapy? Results of a Randomized Study With 15 Years of Follow-Up

PURPOSE Axillary dissection is the standard management of the axilla in invasive breast carcinoma. This surgery is responsible for functional sequelae and some options are considered, including axillary radiotherapy. In 1992, we published the initial results of a prospective randomized trial comparing lumpectomy plus axillary radiotherapy versus lumpectomy plus axillary dissection. We present an update of this study with a median follow-up of 180 months (range, 12 to 221 months). PATIENTS AND METHODS Between 1982 and 1987, 658 patients with a breast carcinoma less than 3 cm in diameter and clinically uninvolved lymph nodes were randomly assigned to axillary dissection or axillary radiotherapy. All patients underwent wide excision of the tumor and breast irradiation. RESULTS The two groups were similar for age, tumor-node-metastasis system stage, and presence of hormonal receptors; 21% of the patients in the axillary dissection group were node-positive. Our initial results showed an increased survival rate in the axillary dissection group at 5 years (P =.009). At 10 and 15 years, however, survival rates were identical in both groups (73.8% v 75.5% at 15 years). Recurrences in the axillary node were less frequent in the axillary dissection group at 15 years (1% v 3%; P =.04). There was no difference in recurrence rates in the breast or supraclavicular and distant metastases between the two groups. CONCLUSION In early breast cancers with clinically uninvolved lymph nodes, our findings show that long-term survival does not differ after axillary radiotherapy and axillary dissection. The only difference is a better axillary control in the group with axillary dissection.

Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review

Clinicians can use biomarkers to guide therapeutic decisions in estrogen receptor positive (ER+) breast cancer. One such biomarker is cellular proliferation as evaluated by Ki-67. This biomarker has been extensively studied and is easily assayed by histopathologists but it is not currently accepted as a standard. This review focuses on its prognostic and predictive value, and on methodological considerations for its measurement and the cut-points used for treatment decision. Data describing study design, patients’ characteristics, methods used and results were extracted from papers published between January 1990 and July 2010. In addition, the studies were assessed using the REMARK tool. Ki-67 is an independent prognostic factor for disease-free survival (HR 1.05–1.72) in multivariate analyses studies using samples from randomized clinical trials with secondary central analysis of the biomarker. The level of evidence (LOE) was judged to be I-B with the recently revised definition of Simon. However, standardization of the techniques and scoring methods are needed for the integration of this biomarker in everyday practice. Ki-67 was not found to be predictive for long-term follow-up after chemotherapy. Nevertheless, high KI-67 was found to be associated with immediate pathological complete response in the neoadjuvant setting, with an LOE of II-B. The REMARK score improved over time (with a range of 6–13/20 vs. 10–18/20, before and after 2005, respectively). KI-67 could be considered as a prognostic biomarker for therapeutic decision. It is assessed with a simple assay that could be standardized. However, international guidelines are needed for routine clinical use.

No significant predictive value of c- erbB-2 or p53 expression regarding sensitivity to primary chemotherapy or radiotherapy in breast cancer

To document whether c‐erbB‐2 over‐expression or p53 accumulation in tumour cells was predictive of response to chemo‐ or radiotherapy, we analyzed a population of patients with breast cancer assigned to neo‐adjuvant therapy (median follow‐up: 54 months). T2/T3‐N0N1b‐M0 tumours (329 cases) were treated either by FAC chemotherapy or by radiotherapy before surgery, and the clinical response was classified as complete or incomplete. Expression of c‐erbB‐2 and p53 was retrospectively evaluated by immunohistochemistry. Proliferation rate was assessed by means of MIB‐1 antibody and by S‐phase fraction. A complete response to chemotherapy was observed in 38/167 patients (23%). Complete response rate was 20% in c‐erbB‐2‐negative tumours, and rose to 31% in tumours with c‐erbB‐2 over‐expression, but this trend was not statistically significant. There was no correlation between p53 staining and response to treatment, whereas chemosensitivity was found correlated with histological grade and S‐phase. A complete response to radiotherapy was observed in 64 of the 156 evaluable patients (41%). Complete response rate was 41% in c‐erbB‐2‐ or p53‐negative tumours, 54% in tumours with c‐erb‐B‐2 over‐expression, and 44% in tumours with p53 accumulation. There was no correlation between response to radiotherapy and histological grade or proliferative rate. No prognostic value was found for c‐erbB‐2 or p53 expression, whereas the 5‐year survival rate was 85% for patients presenting a tumour with a low proliferating index (MIB‐1 < 10%), and 68% for patients presenting a tumour with a high proliferative index. In multivariate analysis, node status (RR = 2), MIB‐1 immunostaining (RR = 2), and tumour size (RR = 1.8) were found to be associated with survival. These results indicate that c‐erbB‐2 or p53 expression is not significantly associated with tumour response to neo‐adjuvant chemo/radiotherapy in our series of breast cancers. Int. J. Cancer (Pred. Oncol.) 79:27–33, 1998.

Familial Invasive Breast Cancers: Worse Outcome Related to BRCA1 Mutations

PURPOSE Although all studies confirm that BRCA1 tumors are highly proliferative and poorly differentiated, their outcomes remain controversial. We propose to examine, through a cohort study, the pathologic characteristics, overall survival, local recurrence, and metastasis-free intervals of 40 patients with BRCA1 breast cancer. PATIENTS AND METHODS A cohort of 183 patients with invasive breast cancer, treated at the Institut Curie and presenting with a familial history of breast and/or ovarian cancer, were tested for BRCA1 germ-line mutation. Tumor characteristics and clinical events were extracted from our prospectively registered database. RESULTS Forty BRCA1 mutations were found among the 183 patients (22%). Median follow-up was 58 months. BRCA1 tumors were larger in size (P =.03), had a higher rate of grade 3 histoprognostic factors (P =.002), and had a higher frequency of negative estrogen (P =.003) and progesterone receptors (P =.002) compared with non-BRCA1 tumors. Overall survival was poorer for carriers than for noncarriers (5-year rate, 80% v 91%, P =.002). Because a long time interval between cancer diagnosis and genetic counseling artificially increases survival time due to unrecorded deaths, the analysis was limited to the 110 patients whose diagnosis-to-counseling interval was less than 36 months (19 BRCA1 patients and 91 non-BRCA1 patients). The differences between the BRCA1 and non-BRCA1 groups regarding overall survival and metastasis-free interval were dramatically increased (49% v 85% and 18% v 84%, respectively). Multivariate analysis showed that BRCA1 mutation was an independent prognostic factor. CONCLUSION Our results strongly support that among patients with familial breast cancer, those who have a BRCA1 mutation have a worse outcome than those who do not.

Conservative treatment of breast cancers by mammaplasty and irradiation : a new approach to lower quadrant tumors

Conservative treatment of breast cancers confined to the lower quadrants often leaves a residual deformity. In order to prevent these poor cosmetic results, 20 patients with lower quadrant cancers have been treated since 1986 at the Institut Curie by wide lumpectomy combined with immediate remodeling of the gland by nipple-bearing superior pedicle mammaplasty and preoperative (9 cases) or postoperative (11 cases) irradiation. The contralateral breast was always rendered symmetrical at the same time. The mean weight of resection was 248 gm, and the resection margins were always free of tumor. The treatment protocols were not modified by the addition of mammaplasty to lumpectomy, and this combination did not induce any significant complications. The mean follow-up was 4.5 years (range 1 to 7.5 years). There was one case of local recurrence; there were four cases of metastases. In this series, the oncologic results were identical to those of conventional treatment by lumpectomy and irradiation. The cosmetic result was good or very good in 75 percent of patients and 91 percent of patients in the group in which mammaplasty was performed prior to irradiation. Treatment of breast cancers by superior pedicle reduction mammaplasty and irradiation is indicated in tumors located in the lower quadrants, whose size in relation to the breast volume is such that conventional conservative treatment by lumpectomy and irradiation would achieve a poor cosmetic result.

Human papillomavirus genotype as a major determinant of the course of cervical cancer.

PURPOSE To determine whether the prognosis of invasive cancers of the uterine cervix is related to the type of human papillomavirus (HPV) associated with the tumor. PATIENTS AND METHODS Two hundred ninety-seven patients with invasive cervical cancer were prospectively registered from 1986 to 1994. HPV typing was performed on DNA extracted from frozen tumor specimens by means of Southern blot hybridization (SBH) and polymerase chain reaction (PCR) techniques. The median follow-up was 38 months. RESULTS HPV sequences were detected in 246 patients (83%): 150 patients had HPV16, 31 patients had HPV18, and 14 patients had one of the intermediate-oncogenic-risk HPV types (HPV31, 33, 35, 52, 58). In 51 patients, HPV type remained undetermined, and in 51 patients, no viral sequences were found. No significant associations were observed between virologic data and tumor stage or node status. The 5-year disease-free survival (DFS) rate was 100% for patients with intermediate-risk HPV-associated tumors, 58% for patients with HPV16-positive tumors, and 38% for patients with HPV18-positive tumors (P = .02). In multivariate analysis, patients with HPV18-associated tumors had a relative risk (RR) of death 2.4 times greater (95% confidence interval [CI], 1.29-4.59) than that for patients with HPV16, and 4.4 times greater (95% CI, 3.48-5.32) than that for patients with a tumor associated with a viral type different from HPV16/18. CONCLUSION The prognosis for invasive cancers of the uterine cervix is dependent on the oncogenic potential of the associated HPV type. HPV typing may provide a prognostic indicator for individual patients and is of potential use in defining specific therapies against HPV-harboring tumor cells.

Prediction of tumour involvement in remaining axillary lymph nodes when the sentinel node in a woman with breast cancer contains metastases

In a significant proportion of women with breast cancer, the sentinel node is the only involved node in the axilla. The purpose of this study was to identify factors associated with histologically positive non‐sentinel lymph nodes.

Donor site sequelae after autologous breast reconstruction with an extended latissimus dorsi flap.

&NA; The indications for autologous reconstruction are increasing. The standard procedure is the transverse rectus abdominis muscle flap; however, this flap has contraindications and drawbacks. The latissimus dorsi muscle flap is simple and reliable. Hokin et al. demonstrated in 1983 that this flap can be extended and used for breast reconstruction without an implant. Since then, it has been widely studied in this setting and is known to provide good aesthetic results. Dorsal sequelae, conversely, were not appraised. The aim of this study was to assess objective and subjective dorsal sequelae after the harvest of an extended flap. Forty‐three consecutive patients who had had breast reconstruction with an autologous latissimus dorsi flap were assessed by a surgeon and a physiotherapist for muscular strength and shoulder mobility. Patient opinion was studied through a questionnaire. Mean delay between the operation and the evaluation was 19 months. Early complications, mainly dorsal seromas, were frequent after the harvest of an extended flap (72 percent). There was no late morbidity and, especially, no flap loss or partial necrosis. As for functional results, 37 percent of the patients had complete adjustment and 70 to 87 percent demonstrated no change in shoulder strength. Sixty percent of the patients experienced no limitation in everyday life, and 90 percent said they would undergo this procedure again. The authors show that dorsal sequelae after an extended latissimus dorsi flap are minimal and that this technique compares favorably with the transverse rectus abdominis muscle flap. (Plast. Reconstr. Surg. 109: 1904, 2002.)