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.

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.

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.

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.

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.

[Models to predict non sentinel lymph node status in breast cancer patients with metastatic sentinel lymph node]. / Modèles prédictifs d'envahissement des ganglions non sentinelles en cas de métastases des ganglions sentinelles dans le cancer du sein.

In breast cancer, nine models have been developed to predict non SN status in patients with SN metastasis. Four models are nomograms: the Memorial Sloan-Kettering Cancer Center nomogram (MSKCC nomogram), the nomogram of Degnim et al. (Mayo nomogram), the nomogram of Pal et al. (Cambridge nomogram), and the nomogram of Kohrt et al. (Stanford nomogram). Three models are scoring systems: the Tenon score, the score from the M.D. Anderson Cancer Center (MDA score), and the score of Saidi et al. Finally, two are recursive partitioning tools developed by Kohrt et al. Before being used in routine, these models have to be validated in independent populations based on discrimination and calibration. However, the main issue is their clinical utility based not only on the low false negative rate but also its potential to discriminate patients with a low risk of non SN involvement. Several institutions have tested the MSKCC nomogram, with AUC ranging from 0.58 to 0.86. It was not validated by four studies which did not recommend its use even in patients with micrometastasis.The external validation of the Tenon score confirmed its relevance with an AUC of 0.82.

[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.

The sentinel lymph node procedure for patients with preoperative diagnosis of ductal carcinoma in situ: risk factors for unsuspected invasive disease and for metastatic sentinel lymph nodes.

BACKGROUND: Occult invasive disease could be found at definitive histology in patients initially diagnosed with large ductal carcinoma in situ (DCIS). Sentinel lymph node (SLN) biopsy is a reliable and minimally invasive procedure providing axillary information and avoiding a second operation in this particular group of patients. The aim of our study was to assess the value of SLN biopsy in patients with large DCIS who are at highest risk for being upstaged to invasive carcinoma. PATIENTS AND METHODS: The study included 195 patients diagnosed with DCIS upon initial core biopsy and undergoing SLN biopsy. Many features were correlated with the presence of unsuspected invasive disease and positive SLN biopsy using univariate and multivariate analyses. RESULTS: Of the 110 patients with pure DCIS, seven patients (6%) had a metastatic lymph node; 31 patients (16%) were found to have invasive disease upon final histology. Univariate analysis of predictors of unsuspected invasive carcinoma showed that patients having a preoperative biopsy that indicated DCIS with microinvasion (DCISM) or large DCIS were at a higher risk of invasive carcinoma after histological examination of the operative specimen. Of the 31 patients who were upstaged to invasive carcinoma at final histology, seven patients (22%) had a positive SLN biopsy. The analysis of predictors of positive SLN in our study shows that diffuse DCIS requiring mastectomy is the main risk factor for SLN metastasis. CONCLUSION: There are no real predictive factors for invasive disease in patients with an initial diagnosis of DCIS or DCISM. Our study supports the value of SLN biopsy in patients with a preoperative DCISM biopsy or patients with a large pure DCIS biopsy requiring mastectomy.

[Synchronous bilateral breast cancer: risk factors, diagnosis, histology and treatment]. / Cancers du sein bilatéraux synchrones: facteurs de risque, diagnostic, histologie, traitement.

OBJECTIVE: Synchronous bilateral breast carcinoma (SBBC) is not uncommon. Women with unilateral breast carcinoma are at increased risk for developing contralateral disease. The purpose of this study was to evaluate risk factors, diagnostic circumstances, histological characteristics and therapeutic methods for SBBC. PATIENTS AND METHODS: Between July 1992 and May 2006, 62 patients with SBBC were treated at Tenon hospital (Paris, France). Population was divided into two sub-groups corresponding with two successive periods. Epidemiological characteristics, diagnostic circumstances, therapeutic methods and histological characteristics were analysed. RESULTS: Global incidence of SBBC during this period was 2.6%. The patients presenting a CSBS had a family antecedent of breast cancer in 23.7% of the cases. The most frequent situation associated a palpable tumour and an infraclinic contralateral lesion (43.5%). MRI made diagnosis possible in seven tumours. Among the patients 38.7% had a bilateral mastectomy and 33.9% profited from the technique of the ganglion sentinel. The proportions of invasive lobular carcinomas and the multifocal tumours were 17.7%. The tumours had the same histological type in 78.3% of the cases and the expression of oestrogen receptors was identical in 91.4% of the cases. DISCUSSION AND CONCLUSION: The principal risk factors of CSBS are a family history of breast cancer, the histological type lobular invasive and the multifocal character of the first tumour. A conservative surgery is possible as well as the use of the technique of the ganglion sentinel. The CSBS have histological similarities, probably due to environmental factors.

[Guidelines for the follow-up of women treated for high-grade cervical neoplasia]. / Recommandations pour la surveillance des patientes traitées pour des lésions de haut grade du col utérin.

The women treated for CIN2-3 remain at a substantially increased risk of recurrences, which persists longer than 10 years. The women treated for a CIN2-3 are more likely to develop invasive cancer and the risk is two to five times greater than that of the general population. The main objective of the follow-up of patients treated for high-grade CIN is in one hand, to detect and treat the recurrences and on the other hand, to determine a subpopulation presenting a high risk of recurrence which should be followed-up more intensively. At present, frequent follow-up with cytology and colposcopic evaluation of the cervix is the preferred strategy recommended in France by Anaes. Both, the cytology and the colposcopy don't have a very good sensitivity. HPV test is more sensitive compared to cytology or colposcopy in detecting CIN treatment failures. It would be more prudent to use a strategy involving both the cytology and HPV test. Both the sensitivity and the negative predictive value of combined cytology and HPV testing in detecting a residual disease or recurrence are around 100%. Women presenting negative results of both tests, could, then be considered at a low risk of recurrence and their surveillance should be the same as that of the screening of the general population. In case of positivity a more intensive follow-up should be organized.

[Risk of breast cancer related to pregnancy]. / Risque de cancer du sein lié à la grossesse.

After a pregnancy, there is a transitory increase in the risk of breast cancer. During the pregnancy, the number of mammary epithelial cells increases massively. This increase seems partly due to the expansion of stem cells and proliferating intermediate cells. This proliferation of epithelial cells is accompanied by angiogenesis and by recruitment of stromal cells, as well as changes of the extracellular matrix. During any pregnancy, there is cell trafficking between mother and foetus. Hematopoietic or mesenchymal foetal stem cells are transferred in maternal circulation and could be used by the tumor as support cells and take part in the tumoral development. The study of the mechanisms of this specific oncogenesis may help to develop chemoprevention strategies.

The sentinel node concept in endometrial cancer: histopathologic validation by serial section and immunohistochemistry.

BACKGROUND: The sentinel node (SN) is defined as the first node in the lymphatic system that drains a tumor site. If the SN is not metastatic, then all other nodes should also be disease-free. We used serial sections and immunohistochemical (IHC) staining to examine both SN and non-sentinel nodes (non-SNs). PATIENTS AND METHODS: Twenty-three patients (median age 69 years) with early endometrial cancer underwent a laparoscopic SN procedure based on a combined detection method, followed by complete laparoscopic pelvic lymphadenectomy. If the SN was free of metastasis by both hematoxylin and eosin (H&E) and IHC staining, all non-SNs were also examined by the combined staining method. RESULTS: SNs were identified in 19 patients (82.6%). A total of 47 SNs were removed (mean 2.5). Ten SNs (21.3%) from five patients (26.3%) were found to be metastatic at the final histologic assessment. In 14 patients, no metastatic SN involvement was detected by H&E and IHC staining. In these 14 patients, 120 non-SNs were examined by serial sectioning and IHC, and none were found to be metastatic. CONCLUSION: The SN procedure appears to reliably predict the metastatic status of the regional lymphatic basin in patients with early endometrial cancer.

Unscarred uterine rupture--case report and literature review.

BACKGROUND: Spontaneous uterine rupture is a life threatening event, and the diagnosis is difficult in an unscarred uterus. Many factors can help prevent the catastrophic consequences. CASE: A 38-year-old multipara in labor was admitted at 39.5 weeks of gestation. Ultrasound suggested a macrosomic fetus but the cervix was well dilated. Labor was immediately monitored. Two hours later, the fetus developed progressive heart rate decelerations. While evaluating the unexplained anomaly, epigastric pain and vaginal bleeding prompted emergency cesarean delivery. The uterine tear was repaired with good evolution but the infant died a few days later. CONCLUSION: The association of multiparity, uterine distension and active labor could be considered as risk factors of uterine rupture in cases of unexplained anomalies in an unscarred uterus, making a catastrophic event preventable.

[Value of sentinel lymph node procedure in endometrial cancer]. / La recherche du ganglion sentinelle dans le cancer de l'endomètre a-t-elle un intérêt?

In cancer research, regional lymph node status is a major prognostic factor and a decision criterion for adjuvant therapy. The sentinel node procedure, which has emerged to reduce morbidity of extensive lymphadenectomy, remains a major step in the surgical management of various cancers. Sentinel node procedure has become a standard technique for the determination of the nodal stage of the disease in patients with melanoma, vulvar cancer and in breast cancer. In endometrial cancer, the sentinel node biopsy is still at the stage of feasibility. In this article, we review the technical aspects, results, clinical implications and limitations of sentinel node procedure in endometrial cancers.

[Sentinel node biopsy in invasive breast cancer in 2007]. / Prélèvement du ganglion sentinelle dans le cancer invasif du sein en 2007.

Sentinel lymph node (SN) biopsy for breast cancer has been introduced in the mid-1990s and it has now been performed on thousands of patients. This procedure has been rapidly adopted around the world by surgical specialists in clinical practice as a diagnostic procedure instead of the axillary lymph node dissection. The diffusion of the SN mapping in routine must be careful by respecting some principles of methodology and especially of training, in order to maintain its irreversible development. However, the advent of this mini-invasive technique revealed new questions, which the concept of the SN procedure raises: can we increase the current indications? Could axillary lymph node dissection be avoided in patients with metastatic SN? What is the morbidity of the biopsy of the SN? Which is the prognostic value of micrometastatis discovered by the diffusion of the ultra-stadification of the SNs? The GS procedure is a diagnostic method the reliability of which is now on accepted in its usual indications (tumours in place, small size breast tumour without palpable adenopathy). The value of the axillary dissection after metastatic SN is the subject of debates and controversies although axillary dissection remains recommended. So the use of scores or predictive nomograms is currently developed to select the patients being able not to justify of complementary axillary dissection, and seems promising.

[Sentinel node biopsy in cervical cancer: state-of-the-art in 2007]. / Biopsie du ganglion sentinelle dans le cancer du col de l'utérus: état de l'art en 2007.

In cervical cancer, lymph node status is a major prognostic factor and a decision criterion for adjuvant therapy warranting the lymphadenectomy. The sentinel node procedure, which has emerged to reduce morbidity of extensive lymphadenectomy, remains a major step in the surgical management of solid cancers. Sentinel node procedure has become a standard technique for the determination of the nodal stage of the disease in patients with melanoma, vulvar cancer and recently in breast cancer. In cervical cancer, the sentinel node biopsy is still at the stage of feasibility. In this article, we review the technical aspects, results and clinical implications of sentinel node procedure in cervical cancer.

[Surgical management of breast microclacifications]. / Stratégie de prise en charge chirurgicale des microcalcifications du sein.

The breast infraclinic lesions, as microcalcifications, are images found very often within the framework of the tracking of the breast cancer. The majority of them correspond to benign lesions. The therapeutic strategy of these microcalcifications depends on the evaluation of the degree of suspicion of the image which classification BI-RADS makes it possible to make more precise and more reproducible. In certain cases where a histological diagnosis is necessary, the macrobiopsies make it possible to limit the surgery to the only cases where the antomo-pathological analysis impose it. Thus, the percutaneous procedure performed under local anaesthesia give the possibility of avoiding an useless intervention for a benign lesion, or of avoiding, for a malignant lesion, an operational time with aiming diagnoses followed by a therapeutic surgical recovery. The stereotaxic percutaneous procedures, by confirming a invasive malignant lesion, also follow to perform sentinel lymph node biopsy, or to program an axillary dissection. It also can in the event of large infraclinic lesion, confirmed by two macrobiopsies spaced of more than 3 cm, to perform a mastectomy associated to immediate breast surgical reconstruction.

[Is axillary lymph node dissection always necessary in breast cancer patients with a positive sentinel node?]. / Ganglion sentinelle métastatique d'un cancer du sein: peut-on éviter le curage axillaire complémentaire?

Axillary lymph node dissection (ALND) is recommended for patients with breast cancer metastasis to a sentinel lymph node (SLN). However in 40-70% of cases, the SLN may be the only area of metastasis in the dissected axillary contents. In patients with a positive SLN, independently predictive factors for non-SLN metastasis include size of the primary tumor, the size of the SLN metastases, extracapsular extension, and the proportion of positive SLN's among all identified SLNs. Some authors have developed scores and nomograms to estimate a patient's risk for non-SLN metastases. These scores and nomograms should be applied prospectively to a large numper of SLN positive patients who thereafter undergo completion ALND. It is necessary to verify the predictive validity of these scores before we recommend the abandonment of ALND in patients with a very low likelihood of non-SLN metastasis. In this article we review the various predictive factors of non-SLN involvement and the scores or nomograms which have been developed to predict the likelihood of a positive ALND after a positive SLN biopsy.