Characteristics and clinical outcome of T1 breast cancer: a multicenter retrospective cohort study.

BACKGROUND: A subgroup of T1N0M0 breast cancer (BC) carries a high potential of relapse, and thus may require adjuvant systemic therapy (AST). PATIENTS AND METHODS: Retrospective analysis of all patients with T1 BC, who underwent surgery from January 1999 to December 2009 at 13 French sites. AST was not standardized. RESULTS: Among 8100 women operated, 5423 had T1 tumors (708 T1a, 2208 T1b and 2508 T1c 11-15 mm). T1a differed significantly from T1b tumors with respect to several parameters (lower age, more frequent negative hormonal status and positive HER2 status, less frequent lymphovascular invasion), exhibiting a mix of favorable and poor prognosis factors. Overall survival was not different between T1a, b or c tumors but recurrence-free survival was significantly higher in T1b than in T1a tumors (P = 0.001). In multivariate analysis, tumor grade, hormone therapy and lymphovascular invasion were independent prognostic factors. CONCLUSION: Relatively poor outcome of patients with T1a tumors might be explained by a high frequency of risk factors in this subgroup (frequent negative hormone receptors and HER2 overexpression) and by a less frequent administration of AST (endocrine treatment and chemotherapy). Tumor size might not be the main determinant of prognosis in T1 BC.

How to measure breast cancer tumoral size at MR imaging?

OBJECTIVE: To compare the accuracy of different MR sequences to measure tumor size. METHODS: Eighty-six women (mean age: 53 years (30-78)) who underwent preoperative MRI for breast cancer were included. Maximal diameters of the index tumor (IT) and of the whole extent of the tumor (WET) were measured on T2-weighted (T2W) sequences, on dynamic contrast-enhanced (DCE) T1-weighted (T1W) sequences and on Maximal Intensity Projection (MIP) reconstructions. Agreements with pathological size were evaluated using concordance correlation coefficient (k). RESULTS: Median pathological size of IT was 20mm (13-25 mm, interquartile range). Median pathological size of the WET was 29 mm (16-50mm, interquartile range). Measurement of IT showed a good concordance with pathological size, with best results using T2W (k = 0.690) compared to MIP (k = 0.667), early-subtracted DCE frame (k = 0.630) and early-native DCE frame (k = 0.588). IT was visible on T2W in 83.7% and accurately measured within 5mm in 69.9%. Measurement of WET was superior using early-subtracted DCE frame (k = 0.642) compared to late-native frame (k = 0.635), early-native frame (k = 0.631), late-subtracted frame (k = 0.620) and MIP (k = 0.565). However, even using early-subtracted frame, WET was accurately measured within 5mm only 39.3%. CONCLUSION: If visible, IT size is best measured on T2W with a good accuracy (69%) whereas WET is best estimated on early-subtracted DCE frame. However, when adjacent additional sites exist around IT, suspected surrounding disease components need to be proved by pathological analysis.

Which breast cancer decisions remain non-compliant with guidelines despite the use of computerised decision support?

BACKGROUND: Despite multidisciplinary tumour boards (MTBs), non-compliance with clinical practice guidelines is still observed for breast cancer patients. Computerised clinical decision support systems (CDSSs) may improve the implementation of guidelines, but cases of non-compliance persist. METHODS: OncoDoc2, a guideline-based decision support system, has been routinely used to remind MTB physicians of patient-specific recommended care plans. Non-compliant MTB decisions were analysed using a multivariate adjusted logistic regression model. RESULTS: Between 2007 and 2009, 1624 decisions for invasive breast cancers with a global non-compliance rate of 8.3% were analysed. Patient factors associated with non-compliance were age>80 years (odds ratio (OR): 7.7; 95% confidence interval (CI): 3.7-15.7) in pre-surgical decisions; microinvasive tumour (OR: 5.2; 95% CI: 1.5-17.5), surgical discovery of microinvasion in addition to a unique invasive tumour (OR: 4.2; 95% CI: 1.4-12.5), and prior neoadjuvant treatment (OR: 4.2; 95% CI: 1.1-15.1) in decisions with recommendation of re-excision; age<35 years (OR: 4.7; 95% CI: 1.9-11.4), positive hormonal receptors with human epidermal growth factor receptor 2 overexpression (OR: 15.7; 95% CI: 3.1-78.7), and the absence of prior axillary surgery (OR: 17.2; 95% CI: 5.1-58.1) in adjuvant decisions. CONCLUSION: Residual non-compliance despite the use of OncoDoc2 illustrates the need to question the clinical profiles where evidence is missing. These findings challenge the weaknesses of guideline content rather than the use of CDSSs.

[Are decisions of multidisciplinary tumor boards in accordance with the guidelines? Experience of an university reference center for breast cancer]. / Les décisions des RCP sont-elles conformes au référentiel utilisé ? Expérience d'un centre de référence universitaire pour le cancer du sein.

OBJECTIVE: Multidisciplinary meeting (MDM) should ensure a homogeneous management of the patients by following breast cancer guidelines. Are these guidelines really applied in MDM decisions? PATIENTS AND METHODS: We reviewed the last 200 cases of patients operated in our department for breast cancer. We searched for each case if MDM had been consulted, at which step of the management and if the decision was in accordance with our guidelines. RESULTS: Mean age of the 200 patients was 56 (range 27-87)years old and 145 of them (72,5%) had an invasive breast cancer. All cases were presented to the MDM, 148 (74%) preoperatively and 200 (100%) postoperatively. Only four decisions did not follow our guidelines. In three cases, the decision was explained within the MDM report and in one case, the decision was not explained but could be understood. DISCUSSION AND CONCLUSION: We found a significant relation between MDM decisions and our guidelines. However, complex cases require adapting the guidelines to the particularity and the wishes of the patients.

Germline RAD51C mutations in ovarian cancer susceptibility.

Several genes might explain BRCA1/2 negative breast and ovarian family cases. Deleterious mutations in few genes involved in the Fanconi complex are responsible for Fanconi anemia at the homozygous state and breast cancer (BC) susceptibility at the heterozygous state (BRCA2, PALB2, BRIP1). RAD51C plays an important role in the double-strand break repair pathway and a biallelic missense mutation in the RAD51C gene was found in a Fanconi anemia-like disorder. Subsequently, six monoallelic pathogenic mutations were identified after screening 480 BRCA1/2 negative breast and ovarian cancer (BC/OC) pedigrees. Several reports were unsuccessful to replicate these results. To investigate whether germline mutations in RAD51C are associated with an increased risk of developing BC/OC, we screened, by Sanger sequencing of the coding sequence, 117 index cases of breast and ovarian families from French or European origin, and negative for BRCA1/2 mutations. In our study, we found 3 pathogenic mutations among 117 families screened which corresponds to a 2.6% frequency. Our results confirm that RAD51C is a susceptibility gene for ovarian and BC and that this gene should be screened for mutations in families with multiple BC/OC.

Predictive factors for breast cancer in patients diagnosed with ductal intraepithelial neoplasia, grade 1B.

BACKGROUND: For ductal intraepithelial neoplasia, grade 1B, studies that predict breast cancer risk after an 11-gauge vacuum-assisted breast biopsy have yielded contradictory results. In order to identify a predictive model of breast cancer risk, we assessed the underestimation rate according to radiological and clinical findings. PATIENTS AND METHODS: Our study involved 212 patients. We compared the area under the receiver operating characteristic curves and the clinical utility of a logistic regression and partitioning model. RESULTS: Overall upgrade to malignancy occurred in 42 (19.8%) out of the 212 cases. The area under the curve for the logistic regression and partitioning model were 0.65 (95% confidence interval=0.61-0.70) and 0.58 (95% confidence interval=0.54-0.62), respectively. The lowest predicted underestimation rate obtained with the logistic regression model was 9.5%. CONCLUSION: From this large series, we were unable to define any accurate safety model for breast cancer. Surgery should be thus recommended.

Scoring to predict the possibility of upgrades to malignancy in atypical ductal hyperplasia diagnosed by an 11-gauge vacuum-assisted biopsy device: an external validation study.

BACKGROUND: Ko's scoring system was developed to predict malignancy upgrades in patients diagnosed with atypical ductal hyperplasia by core needle biopsy. The Ko algorithm was able to identify a subset of patients who were eligible for exclusively clinical follow-up. The current study statistically investigated the patient outcomes to determine whether this scoring system could be translated and used safely in clinical practice. METHODS: We tested the statistical performance of the Ko scoring system against an external independent multicentre population. One hundred and seven cases of atypical ductal hyperplasia diagnosed by an 11-gauge biopsy needle were available for inclusion in this study. The discrimination, calibration and clinical utility of the scoring system were quantified. In addition, we tested the underestimation rate, sensitivity, specificity, and positive and negative predictive values according to the score threshold. RESULTS: The overall underestimation rate was 19% (20/107). The area under the receiver operating characteristic curve for the logistic regression model was 0.51 (95% confidence interval: 0.47-0.53). The model was not well calibrated. The lowest predicted underestimation rate was 11%. The sensitivity, specificity, positive predictive value, and negative predictive values were 90%, 22%, 20%, and 89%, respectively, according to the most accurate threshold proposed in the original study. CONCLUSION: The scoring system was not sufficiently accurate to safely define a subset of patients who would be eligible for follow-up only and no additional treatment. These results demonstrate a lack of reproducibility in an external population. A multidisciplinary approach that correlates clinicopathological and mammographic features should be recommended for the management of these patients.

[Prognostic and predictive factors in multifocal breast carcinoma]. / Facteurs prédictifs et pronostiques des cancers du sein multifocaux.

OBJECTIVES: Multicentricity is not listed as a major prognostic parameter in invasive breast carcinoma, and is not by itself an indication of systemic adjuvant treatment. Furthermore, evaluating the size of these tumors is discussed. The aims of this study are to evaluate prognostic value of multicentricity, and to compare different way for measuring multicentric breast carcinomas. PATIENTS AND METHODS: Between 2001 and 2008, 1458 patients having breast invasive carcinoma were included in Tenon Hospital, Paris, France; 16% had a multicentric cancer. We have compared impact of multicentricity on lymph node (LN) involvement, and compared 3 ways for measuring these cancers. RESULTS: LN involvement was significantly associated with multicentricity. We found an over-risk of 20% for LN involvement in patients having multicentric cancer, whatever the size of the tumors. Considering the diameter of the largest focus is the best way for measuring these cancers. DISCUSSION AND CONCLUSION: We did not find a subgroup of patients at low risk of LN involvement when having a multicentric breast cancers. These results lead us to extend indications of adjuvant chemotherapies in all multicentric breast cancer. These results should be validated by randomized prospective studies.

Interest in cavity shaving in breast conservative treatment does not depend on lumpectomy technique.

In breast conserving surgery (BCS), the usefulness to perform systematic cavity shaving is actively debated. Some investigators argued that systematic cavity shaving could avoid surgical re-excision and make diagnosis of unexpected multifocality. Others argued that usefulness of cavity shaving depends on volumes of resection. In this study one hundred patients undergoing BCS with systematic cavity shaving were included. Margins less than 3 mm were considered to be insufficient. We tested clinico-pathological characteristics in order to identify predictive model of cavity margin shaving utility and we sought to determine if cavity margin shaving usefulness depends on volumes of resection. We showed that cavity shaving avoids the need for re-excision in 24% of cases as well as diagnosis of multifocality in 6% of cases. However, the clinical usefulness of cavity shaving was not related to the volumes of resection.

Pregnancy-associated breast cancer is as chemosensitive as non-pregnancy-associated breast cancer in the neoadjuvant setting.

BACKGROUND: The aim of this study was to determine the chemosensitivity of pregnancy-associated breast cancer (PABC) in the neoadjuvant setting by comparing the observed pathological complete response (pCR) rate with the rate predicted by a validated nomogram. METHODS: Data from 48 PABC patients who received neoadjuvant chemotherapy (NACT) were collected. To predict the response rate to chemotherapy, we used well-calibrated logistic regression-based nomograms to calculate individual probability of pCR. RESULTS: Observed rates of pCR were concordant with predictions in the whole sample and in the analyzed subgroups. For the whole sample, the area under the receiver-operated curve (AUC) was 0.77 (95% CI 0.66-0.87). The calibration of predicted and observed probabilities was excellent. In the subgroup analyses (NACT initiated during pregnancy or postpartum, NACT with only anthracycline or both anthracycline and taxanes), discriminations assessed by AUC were significantly above 0.5, except for patients treated with anthracycline only. The interpretation was limited by a lack of power. CONCLUSION: Through the use of nomograms, our study demonstrates that PABC is as chemosensitive as non-PABC and suggests that taxanes should be part of the NACT regimen for PABC. Further studies are warranted to increase the power of the presented data.

[Clinicopathological and genomics predictors of response to neoadjuvant chemotherapy in breast cancer]. / Prédicteurs clinicopathologiques et génomiques de la réponse à la chimiothérapie néoadjuvante dans les cancers du sein.

Breast cancer is a frequent and heterogeneous disease. The choice of systemic treatments such as chemotherapy is based on predicting factors of response that did not much evolve. Preoperative chemotherapy provides an opportunity to directly assess tumor response to therapy. Predictors based on mathematical models could optimize those treatments. To go on this way, three different concepts have been developed to predict the preoperative chemotherapy complete response. Predictors based on clinical and pathological variables are specific of a tumor. They combine into mathematical models variables that have been previously identified as predicting the preoperative chemotherapy complete response. Predictors based on gene expression profile have been developed from groups of patients who received preoperative chemotherapy. They integrate multigene information to predict the tumor behaviour in front of several cytotoxic agents. Those predictors developed for each type of drug characterize the genetic chemoresistance of a tumor. In the same time, predictors of chemosensitivity developed from cell lines of diverse human cancer appeared. The authors established a genetic profile involved into chemoresistance and extrapolated the drug sensitivity for another type of cancer which was not represented, as breast cancer. All those predictors seem interesting but evolution of patients' characteristics and treatments induces a perpetual reassessment to optimize our predictive abilities.

The role of lymph node resection in ovarian cancer: analysis of the Surveillance, Epidemiology, and End Results (SEER) database.

OBJECTIVE: The therapeutic role of lymphadenectomy on the survival in patients with ovarian cancer is controversial. The aim of this study was to evaluate the survival impact of lymphadenectomy, depending on the disease stage and extent of the surgery. DESIGN: The surveillance, epidemiology, and end results (SEER) registry provided ovarian cancer data from 17 registries. SETTING: Surveillance, Epidemiology, and End Results database. POPULATION: The study population comprised 49,783 patients. METHODS: Survival was studied according to the number of lymph nodes removed, with stratifications on disease stage and extent of surgery. MAIN OUTCOME MEASURE: The 5-year cause-specific survival rate. RESULTS: The median follow up for patients alive at the last follow-up visit was 39 months. The five-year cause-specific survival rates were 37, 62, and 71% for the groups in which no lymph nodes were examined, in which between one and nine nodes were examined, and in which ten or more nodes were examined, respectively (P< 0.001). Avoiding lymphadenectomy was deleterious in all stages of the disease. It was maximal for International Federation of Gynecology and Obstetrics (FIGO) stage-II patients, but there was no significant interaction between stage and extent of lymphadenectomy. The cause-specific survival was found to significantly increase when more nodes were resected, even if the surgical procedure consisted of debulking surgery or a pelvic exenteration. CONCLUSION: Our study suggests a beneficial effect of lymphadenectomy in epithelial ovarian tumours, regardless of the stage of disease and extent of surgery. However, potential biases inherent to this retrospective methodology, such as staging migration, defining the extent of residual disease, and the possibility that thorough lymphadenectomy may reflect the quality of cytoreductive surgery, preclude any formal conclusions on the therapeutic role of lymphadenectomy.

[Modalities for the functionning of a Care Center for women at high risk for breast and ovarian cancers: The French experience of Tenon Hospital]. / Modalités de fonctionnement d'un centre de suivi des femmes à haut risque de cancer du sein et de l'ovaire : une expérience à l'hôpital Tenon.

High risk may be defined as either an absolute risk greater than 20 % or a relative risk greater than 4. Concerning breast and ovarian cancer, high risk patients include carriers of a constitutive deleterious mutation of BRCA1 or BRCA2 genes, patients with a significant family history of breast or ovarian cancer, and patients who have been diagnosed a benign breast lesion with a high risk of degeneration, i.e. atypical hyperplasia. Following up such patients relies on specific strategies. A center including a large panel of physicians involved in the various modalities for patients' management (geneticians, radiologists, gynecologists, plastic surgeons, pathologists, endocrinologists, psychologists, medical oncologists) has been created at Tenon Hospital with this purpose. The collaboration of these different specialists with the referent physician of the patient allows for the definition and the implementation of a patient-centered follow-up continuously updated to take into account the different periods of a woman's life, according to best practices recommendations and the evolving state-of-the art.

Histology after lumpectomy in women with epithelial atypia on stereotactic vacuum-assisted breast biopsy.

BACKGROUND: Large-core needle biopsy of the breast (LCNB) and vacuum-assisted breast biopsy (VABB) are widely used as alternatives to open surgical biopsy (OSB) for initial diagnosis of mammographic abnormalities. Between 18% and 80% of cases in which such specimens show atypical lobular hyperplasia (ALH) or atypical ductal hyperplasia (ADH) are found to be malignant at surgery. DESIGN: From 1999 to 2005, 68 women with mammographic abnormalities were sampled by stereotactic VABB and presented atypical epithelial hyperplasia. Immunohistochemical staining with anti-cytokeratin 5/6 and anti-E-cadherin antibodies was performed. All women underwent a lumpectomy. Clinical, radiological or histological factors predictive of the risk of finding malignancy at surgery were sought. RESULTS: VABB initially showed 28 cases of ADH, 32 cases of ALH, one case of flat epithelial atypia, five cases of mixed atypia, and two cases of Lobular Carcinoma In Situ (LCIS). After slide review with immunohistochemical staining, two cases of ADH were reclassified as simple hyperplasia and two cases of ALH were reclassified as mixed atypia. Seven lesions (10.3%) that appeared to be benign on VABB were found to be malignant on OSB (Ductal Carcinoma In Situ (DCIS) in six cases and invasive ductal carcinoma in one case). ADH was the only predictive factor of malignancy on OSB (p=0.04 versus ALH). CONCLUSION: ADH diagnosed by vacuum-assisted breast biopsy frequently corresponds to cancer on open surgical biopsy. Surgical excision of all breast lesions containing atypical hyperplasia on percutaneous biopsy can be recommended.

[Feasibility of the sentinel node biopsy in breast cancer in case of histological multifocality diagnosis]. / Faisabilité du ganglion sentinelle dans le cancer invasif du sein en cas de découverte histologique de la multifocalité.

OBJECTIVES: The use of sentinel node biopsy (SNB) has replaced axillary lymph node dissection (ALND) as the new standard of care in early unifocal breast cancer. In multifocal breast cancer, this procedure remains controversial. The real problem is when a multifocal tumor is discovered during or after the surgery, with a SNB negative which has been already done. Should we do an additional ALND or not? PATIENTS AND METHODS: We performed a retrospective study of 43 multifocal breast cancer patients who underwent SNB. RESULTS: The mean histological primary tumor size was 16.8 mm (range, 1-52 mm). The mean number of SN removed was 2.07 (range, 1 to 5). Sixteen (34.1%) of the 43 patients had at least one positive SN. Twenty-seven patients had subsequent axillary dissection. Negative predictive value of SN procedure was 100% (95% confidence interval: 87.1-100%) with a FN rate of 0%. Moreover, not any patient has developed axillary recurrence with a mean follow-up of 20.8 months (1-77). DISCUSSION AND CONCLUSION: Our data are not powerful enough to validate the SNB in multifocal breast tumor discovered after an initial surgery. However, the FN rate of 0% is encouraging and prospective studies with a systematic ALND can help surgeons to respond to the question.

[Non-masslike enhancement on breast MRI: interpretation pearls]. / Le rehaussement sans masse en IRM mammaire: comment j'interprète?

The MR Breast Imaging Reporting and Data System (BI-RADS) lexicon of the American College of Radiology (ACR) includes a new lesion category defined as non-masslike enhancement. The purpose of this paper is to review the definition of this new entity, illustrate the main imaging features described in the BI-RADS lexicon and to propose a diagnostic approach based on data from the literature in order to achieve diagnosis and optimal patient management.

Accuracy of stereotactic vacuum-assisted breast biopsy with a 10-gauge hand-held system.

OBJECTIVE: The aim of this study is to evaluate the accuracy and the safety of stereotactic vacuum-assisted breast biopsy with a 10-gauge hand-held portable system. MATERIALS AND METHODS: Retrospective data review of 288 consecutive breast lesions that underwent stereotactic 10-gauge hand-held portable vacuum-assisted biopsy from October 2004 through March 2006, was performed. The mean number of core specimens and the percentage of complete radiological removal of the target lesion were analysed. ADH and DCIS under-estimation were evaluated, as were the immediate and delayed complications due to the procedure. RESULTS: The mean number of core specimens obtained per procedure was 9 (range 4-24). Complete radiological excision of the target lesion was achieved in 31.6% (91 of 288) with 91% of these lesions smaller than 10mm (mean size 7 mm; range 4-20mm). Under-estimation of ADH and DCIS was 18.2% (2 of 11) and 19.2% (9 of 47), respectively. There was no false negative result within a 3-year follow-up (from 2005 till date). Complications were mild and consisted of immediate bleeding and delayed haematomas. CONCLUSION: Breast biopsy using 10-gauge vacuum system is an accurate and safe technique for sampling non-palpable breast lesions.