En el caso de Francia, el cáncer de mama afecta a 58.000 nuevas mujeres al año. Es responsable de 12.000 fallecimientos. Si bien la incidencia sigue aumentando, pero a un ritmo más lento que antes, la mortalidad está disminuyendo a un ritmo regular. Los principales factores de riesgo para desarrollar cáncer de mama son la edad, el país de nacimiento y los antecedentes familiares de cáncer de mama, sobre todo si se ha identificado un contexto genético. La densidad radiológica de la glándula mamaria también parece ser un factor importante, pero tal vez no sea independiente de otros factores de riesgo. Las tasas más altas de cáncer de mama se encuentran en América del Norte y en los países de Europa septentrional y occidental, mientras que la incidencia más baja se registra en los países asiáticos y en desarrollo. No existe certidumbre en cuanto a la alimentación, estudiada alimento por alimento o nutriente por nutriente. Seguramente sea necesario un enfoque global (tipo de alimentación). El peso del estilo de vida y el medio ambiente en el sentido más amplio del término es ciertamente importante pero difícil de comprobar. Cabe señalar, sin embargo, que los migrantes adquieren en una o dos generaciones el nivel de riesgo del país donde viven. En cuanto a los factores vinculados a la vida genital (edad de la primera menstruación, menopausia, edad del primer parto, lactancia materna, número de hijos, etc.), son factores de bajo riesgo pero que se suman. Cabe señalar que la mayoría de las mujeres que desarrollan cáncer de mama no tienen factores de riesgo conocidos.

ConclusionThe rate of SP referral and the use of meds were higher in USA cohort versus the cohort from south of Europe.The reasons for these differences might be related to social and cultural differences, rather than availability of medications.

La presence de lymphocytes infiltrant les tumeurs ou TIL est reconnue comme un facteur pronostique pour plusieurs tumeurs solides. Les avancees recentes de l’immunotherapie sont a l’origine d’un regain d’interet pour les parametres immunologiques au cours des cancers.Dans le cas du cancer du sein, l’evaluation des TIL a fait l’objet d’etudes essentiellement en situations adjuvante et neo-adjuvante, avec des resultats discordants selon les sous-types histologiques. Pour certains, les TIL sont des facteurs pronostiques devant faire partie integrante des classifications internationales.L’objectif de cette synthese est de faire le point sur les donnees actuelles, ainsi que sur la place potentielle de l’evaluation des TIL.

Abstract Background: Inflammatory breast carcinomas have poor prognosis even in the absence of evident synchronous metastases. 18F-FDG PET/CT is not recommended in initial staging but could improve the sensibility of synchronous metastases detection and the management of the patients. Objective: To assess factors associated with synchronous metastases in inflammatory breast carcinomas when evaluated by 18F-FDG PET/CT. Methods: Since 2006, initial staging of locally advanced breast carcinomas in our center consisted of 18F-FDG PET/CT in addition to standard laboratory and radiological tests. We reviewed data of patients with inflammatory breast carcinomas treated from 2006 to 2013 who had an initial evaluable18F-FDG PET/CT. Fisher's exact test and logistic model were used to assess factors associated with synchronous metastases. Overall survival was estimated with the method of Kaplan-Meier. Results: Among 353 locally advanced breast carcinomas seen at the breast disease unit, hospital Saint Louis from 04/2006 to 04/2013, we identified 40 inflammatory breast carcinomas. Initial 18F-FDG PET/CT was available for review in 32 inflammatory breast carcinomas. Median age was 57 years (range 38-78), 39% had pre-menopausal status (n = 12), clinical node involvement was found in 87.5% (n = 28). Histological features on biopsy were: ductal invasive carcinoma 91% (n = 29), SBR grade III 72% (n = 23), negative hormonal receptor 75% (n = 24), positive HER2 37.5% (n = 12), triple negative 44% (n = 14). Synchronous metastases were found in 41% of inflammatory breast carcinomas (n = 13), bone (n = 7), liver (n = 6) and mediastinum (n = 4). Synchronous metastases seemed more common in HER2 positive than in HER2 negative inflammatory breast carcinomas (58% vs 30%, p = 0.15). In multivariate analysis, no factor was associated with synchronous metastases. All patients with inflammatory breast carcinomas received neoadjuvant chemotherapy with sequential anthracycline and taxane (16 patients), dose-dense anthracycline and alkylating agent (8 patients), taxane with or without bevacizumab (7 patients) and anthracycline in 1 patient. Trastuzumab was given in all HER2 positive inflammatory breast carcinomas. Clinical response to neoadjuvant chemotherapy was complete in 16.5% (n = 5), partial in 67% (n = 20), stable or progressive in 16.5% (n = 5) and missing for 1 patient. One patient died before response assessment. Thirty patients (94%) underwent radical mastectomy with axillary node dissection. Pathologic complete response in breast and nodes was found in 27.5% (n = 8). Axillary node invasion was found in 45% (n = 13). All positive hormonal receptors patients received endocrine therapy after surgery. With a median follow-up of 33 months, 10 patients died. Median overall survival was 38.8 months (95%CI: 30.3-NA) with no difference between HER2 positive and HER2 negative patients. Conclusion: Synchronous metastases are common in inflammatory breast carcinomas especially in case of HER2 positive tumors. Complete initial staging with 18F-FDG PET/CT could be useful to detect synchronous metastases mainly in bone and liver and thus allowed to adapt further treatment. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-12-13.

The analytical performance of immunochromatographic assay (ICA) is usually determined by the biological activity of antibody and gold nanoparticle conjugates (AuNP probes). However, conventional probes are constructed using the nondirectional coupling method that can cause the improper orientation of antibodies with the poor accessibility of antigen-binding sites. To address these issues, we report a site-specific directional coupling strategy to enhance the bioactivity of AuNP probes through the specific covalent binding of the aldehyde group in the Fc domain of antibodies with the hydrazide group modified on the surface of AuNPs. Through this design, the antibodies can be erected on the AuNP surface to fully expose the Fab domain and achieve the maximized functional availability. Leveraging these AuNP probes as ICA labels, we demonstrate an improved detection of the hepatitis B surface antigen with less used amount of labeled antibody (0.2 mg/pmol AuNPs), shorter reaction time (10 min), better antibody bioactivity, and higher detection sensitivity (2 ng/mL) compared with the carbodiimide method. Overall, this work provides great promise for the design and the construction of high-performance probes to enhance the detection performance of ICA sensors.

Immunohistochemistry (IHC) and fluorescent in situ hybridisation (FISH) are currently the most commonly used methods to assess HER2 status. PCR-based assays allow quantitative determination of HER2 amplification (Q-PCR) or overexpression (Q-RT–PCR), but are not routinely used. We evaluated the relevance of Q-RT–PCR for HER2 status determination. We compared IHC and Q-RT–PCR in 466 breast tumours. In discordant or equivocal cases, five additional methods (IHC with two other antibodies, FISH, silver in situ hybridisation (SISH) and Q-PCR) were combined to determine HER2 status. Two cases with HER2 intra-tumour heterogeneity were further explored by allelic profiles analysis and HUMARA clonality determination after microdissection. We observed 97.3% concordance between Q-RT–PCR and non-equivocal IHC. Twelve out of 466 cases (3%) revealed discordances between the two methods. The power of Q-RT–PCR to predict HER2 status (defined by seven methods) was similar to that of IHC. Although rare, some discordances between techniques might be due to HER2 intra-tumour heterogeneity and we report two examples, one tumour containing two distinct clones, another tumour consisting of HER2 amplified and non-amplified subclones. Q-RT–PCR and IHC are highly concordant methods for HER2 status assessment, and Q-RT–PCR allows a highly reliable quantitative assessment and could be a useful adjunct to IHC.

To examine factors associated with one step surgery in case of non-palpable breast cancer.Clinical data of 152 consecutively diagnosed patients with breast cancer were analyzed retrospectively. Preoperative diagnostic findings were divided in subgroups: mammographically visible mass/microcalcifications/sonographically visible mass/sonographically visible architectural distortion. Correlation between tumor-size, radiologic tumor morphology, quality of localization and number of operation was evulated. For localization exact wire position was defined less than 3 mm apart from the lesion.One hundred and thirty-six patients attempted breast conservation and underwent preoperative tumor localization. Fourteen of 16 patients had mastectomy without preoperative localization. Average tumor size was 12 mm for one-operation, and 17 mm for re-operation. Significant correlation (p < 0.001) was found between one operation and masses visible in mammograms (55/62 (89%) patients) or sonography (53/64 (83%) patients). Significant correlation was found (p < 0.001) between more re-operation and microcalcifications in mammograms (33/89 (37% patients). In 123/138 (89%) cases wire position was central, in 15/138 (11%) cases distance was maximally 10 mm. No significant correlation was found between number of operation and wire position. Re-operation was required in 38 cases.Mammographically or sonographically visible mass, small size of tumors, preoperative percutaneous biopsy and exact preoperative localization are important for a single step procedure for definite surgical treatment, that we found in 74% of the patients.

As compared to conventional axillary dissection, the sentinel node technique is accompanied by reduced morbidity and shorter hospital stay. Based on available data, the use of this technique does not seem to yield higher rates of axillary recurrence. A combination of both radioisotope detection and blue dye increases the identification rate, while also reducing false-negative rate. Surgical results are optimized when preoperative lymphoscintigraphy mapping is obtained in addition to peroperative probe detection. Considering the site of injection, the subareolar injection can be easy to apply even in case of non-palpable tumours, and gives higher count rates. However, the intraparenchymal, peritumoral, injection is necessary to evidence cases of extra-axillary drainage (internal mammary, infra- or supraclavicular) that is present in about 20% of patients. With the advent of hybrid cameras (SPECT-CT), the topography of these extra-axillary nodes can be given with high precision. Use of the sentinel node technique has been accompanied by an increase in the percent of patients with node involvement, due to an increased detection of micrometastases inferior or equal to 2 mm. Following an overview of basic principles, and of the main results with the sentinel node technique we focus the discussion on several points that are still open to debate, such as: 1) which group of patients can benefit from the sentinel node technique? 2) What is the optimal methodology? 3) What is the prognostic significance of micrometastases and of isolated tumour cells? 4) What attention should be given to extra-axillary drainage?

As compared to conventional axillary dissection, the sentinel node technique is accompanied by reduced morbidity and shorter hospital stay. Based on available data, the use of this technique does not seem to yield higher rates of axillary recurrence. A combination of both radioisotope detection and blue dye increases the identification rate, while also reducing false-negative rate. Surgical results are optimized when preoperative lymphoscintigraphy mapping is obtained in addition to peroperative probe detection. Considering the site of injection, the subareolar injection can be easy to apply even in case of non-palpable tumours, and gives higher count rates. However, the intraparenchymal, peritumoral, injection is necessary to evidence cases of extra-axillary drainage (internal mammary, infra- or supraclavicular) that is present in about 20% of patients. With the advent of hybrid cameras (SPECT-CT), the topography of these extra-axillary nodes can be given with high precision. Use of the sentinel node technique has been accompanied by an increase in the percent of patients with node involvement, due to an increased detection of micrometastases inferior or equal to 2 mm. Following an overview of basic principles, and of the main results with the sentinel node technique we focus the discussion on several points that are still open to debate, such as: 1) which group of patients can benefit from the sentinel node technique? 2) What is the optimal methodology? 3) What is the prognostic significance of micrometastases and of isolated tumour cells? 4) What attention should be given to extra-axillary drainage?

Invasive lobular carcinoma accounts for 4 to 10% of breast cancers. The clinical and radiological diagnosis is difficult to make. Its progression is slower than that of ductal cancer, and the prognostic factors are more favourable. Its metastases are more frequently located in the digestive tract and the ovaries. It is more frequently bilateral. Its prognosis is not different from that of infiltrating ductal carcinomas. The choice of therapies depends on the individual characteristics of each patient and of the biological features of each tumour. However, lobular carcinomas seem to be less responsive to chemotherapy.

Le cancer lobulaire infiltrant représente 4 à 10 % des cancers du sein. Son diagnostic clinique et radiologique est difficile. C'est un cancer d'évolution plus lente que le cancer canalaire avec de meilleurs facteurs pronostiques. Il métastase plus souvent au niveau du tractus digestif et des ovaires. Il est plus fréquemment bilatéral. Son pronostic n'est pas différent de celui des cancers canalaires infiltrants. Les décisions thérapeutiques sont fondées sur les particularités individuelles de chaque patiente et sur les caractéristiques biologiques de chaque tumeur. Il semble cependant que les cancers lobulaires soient moins sensibles à la chimiothérapie.

The incidence of lobular cancers in situ is increasing, especially in post-menopausal women. Whereas this form of disease was regarded for a long time as nothing but a risk factor of the occurrence of later infiltrating carcinoma, it now tends to represent a precancerous state whose progression to subsequent infiltrating carcinoma does not inevitably occur. The clinical and radiological diagnosis remains difficult and the choice of therapies varies according to teams, ranging from mere surveillance to mastectomy.

Neodjuvant chemotherapy has been primitively used in locally advanced breast cancer. More recently, indications have been extended to operable lesions. Several randomized trials have compared preoperative chemotherapy with postoperative surgery. None of these studies with anthracyclines have shown benefit in terms of progression free survival and/or overall survival. The rate of breast-conservative surgery seems slightly increased. However, in the NSABP 18 study. there was also a marginally significant increase in local recurrence when patients were converted from mastectomy lumpectomy to as originally planned. The introduction of taxanes in neoadjuvant chemotherapy protocol leads to a better clinical response and a complete histological responses increase when docetaxel is used, In only one study using docetaxel after anthracyclin treatment, a survival benefit is reported but it is a small study; a longer follow up and the updated results of the NSABP B27 trial are needed to confirm the impact of taxotere in the outcome of breast cancer The integration of trastuzumab with taxane based chemotherapy has already shown high rate of histological complete responses. At least. neoadjuvant chemotherapy has the advantage to study biologic predictive factors of chemotherapy response. This article will review data on standard therapeutic and new agents in neoadjuvant treatment.

PURPOSE: To determine the incidence and prognostic significance of eradication of cytologically proven axillary lymph node metastases in breast cancer patients treated with primary chemotherapy. PATIENTS AND METHODS: Between January 1985 and December 1994, 152 breast cancer patients with invasive T1 to T3 tumors and axillary metastases cytologically proven by fine-needle sampling underwent primary chemotherapy followed by lumpectomy or mastectomy, level I and II axillary lymph node dissection, and irradiation. We studied pathologic complete responses (pCRs) of axillary nodes and breast tumors, as well as predictors of distant metastases. RESULTS: Thirty-five patients (23%) had axillary pCRs, and 20 patients (13.2%) had pCRs of primary breast tumors. Scarff-Bloom-Richardson grade 3 tumors (P = .04) and a clinical response to chemotherapy ≥ 50% (P = .003) were associated with negative axillary status at dissection. An initial tumor size ≤ 3 cm (63 patients) was associated with pCR of the primary tumor (P = .02) but not with complete histologic clearance of axillary lymph nodes. The median length of follow-up was 75 months. In the univariate analysis, age greater than 40 years (P = .003), absence of residual nodal disease (P = .01), and pCR of the tumor (P = .05) were associated with better distant disease-free survival. Five-year distant disease-free survival rates were 73.5% ± 14.9% among patients with no involved nodes at the time of surgery and 48.7% ± 9.2% among patients with residual nodal disease. In the multivariate Cox regression analysis, parameters associated with poor distant disease-free survival were age ≤ 40 years (P = .002), persistence of nodal involvement (P = .03), and S-phase fraction greater than 4% (P = .02). CONCLUSION: Our results suggest that axillary status is a better prognostic factor than response of the primary tumor to primary chemotherapy.