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En France, comme dans la plupart des pays occidentaux, le cancer du sein est la première cause de mortalité, avec un nombre annuel de décès proche de 10 000. Chez les femmes, le cancer du sein est celui dont le taux d’incidence est le plus élevé dans la plupart des pays occidentaux. En France, il y a approximativement 35 000 nouveaux cas chaque année. Le taux d’incidence est de 80 pour 100 000 femmes/an. Il existe une disparité géographique dans les taux d’incidence du cancer du sein. Ils sont élevés dans tous les pays développés, à l’exception du Japon et de la Chine. Ajusté sur l’âge, il est le plus élevé aux États-Unis, et le plus bas en Chine, en Inde, au Japon. La France se situe à une position intermédiaire en Europe. L’incidence du cancer du sein est globalement plus faible dans les pays du Sud de l’Europe. Cette disparité géographique ne peut pas être expliquée uniquement par les facteurs génétiques. L’étude des populations migrantes, dont les taux d’incidence du cancer du sein se modifient pour atteindre celui du pays dans lequel elles migrent, a permis de mettre en évidence le rôle des facteurs environnementaux dans l’apparition du cancer du sein. Parmi ceux-là, la part de l’alimentation est estimée à environ 35 % (entre 20 à 60 %, en fonction du site du cancer) [1]. Il existe donc un réel potentiel de prévention du cancer du sein, sous réserve que les aliments protecteurs soient mis en évidence et que les nutriments responsables de ces effets protecteurs soient individualisés.

L’alimentation intervient à différents niveaux dans le déroulement de la maladie cancéreuse : au niveau du risque [1] et au niveau de l’évolution en modifiant le risque de survenue des métastases. L’alimentation influence-t-elle aussi la réponse aux traitements anticancéreux ? À l’appui de cette hypothèse viennent deux observations indirectes réalisées dans le cancer du sein : nos données [2, 3] ainsi que les observations épidémiologiques provenant d’autres travaux [4] ont apporté des arguments supportant l’hypothèse que les lipides alimentaires peuvent influencer la réponse des tumeurs mammaires aux traitements. On sait que la composition des lipides membranaires n’est pas génétiquement déterminée, mais qu’elle dépend des acides gras disponibles aux tissus périphériques. Le type d’acides gras disponibles est influencé par les apports alimentaires. Comme les tumeurs incorporent dans leurs lipides les acides gras disponibles de façon similaire aux autres tissus [5], il est plausible que les habitudes alimentaires (apports alimentaires en acides gras polyinsaturés, vitamines anti ou pro-oxydantes) puissent influencer leur chimiosensibilité en apportant aux cellules tumorales des substrats de peroxydation.

The important factor determining breast cancer outcome is tumor cell sensitivity to cytotoxic agents. Most anticancer drugs lack intrinsic anti-tumor selectivity, provoking adverse effects in healthy nontumor tissues. As a result, drugs cannot always be delivered to the tumor at doses sufficient to induce tumor shrinkage, increasing the risk of the development of cellular drug resistance by tumor cells. Two main approaches are currently being investigated to reduce the toxicity in nontumor tissue by using a prodrug locally delivered through biochemical activation in the tumor environment, and for specifically increasing the sensitivity of tumors to anticancer drugs by modifying the tumor tissue through dietary supplementation. Both approaches have their own limitations that would be alleviated by combining them in order to better treat breast cancers. Specifically, the potential benefit of bringing together a glucuronide prodrug with dietary supplementation using polyunsaturated fatty acids, and in particular the docosahexaenoic acid (22:6n-3), is discussed. This article also addresses the effects of the interaction of docosahexaenoic acid and breast cancer in terms of clinical outcome and mechanistic features.

Prognostic factors are used to help clinical decision-making in selecting the appropriate treatment for individual patients. The purpose of this retrospective study was to identify one or more factors associated with overall survival (OS) and disease-free survival (DFS), in 710 patients with operable breast cancer, subjected to neoadjuvant chemotherapy followed by surgery, radiotherapy and adjuvant treatments. At a median follow-up of 7.6 years, univariate analysis showed that pathological complete response (pCR) was significantly related to survival (p< 0.003), as well as accepted prognostic factors, as SBR and MSBR grades, hormonal receptors or node involvement at surgery, who remained significant in our study (p< 0.001). The revised Nottingham prognostic index (NPI) and related indices (BGI, MNPI and MBGI) were also significantly associated to survival (p< 0.003). In multivariate analysis, node involvement and MSBR grade remained prognostic factors for OS and DFS (p< 0.0003 and p< 0.02, respectively). The MNPI and pCR were significantly related with OS (p= 0.04) and pts with hormonal receptor-positive tumours had a better DFS than others (p= 0.004). Among all clinical and pathological parameters, axillary dissection after neoadjuvant chemotherapy is still important to determine node involvement, a major prognostic factor. Moreover, MSBR grade seemed to be more accurate and predictive of long-term outcome than the standard SBR grade. It is concluded that, outside any other ‘biological’ factor, residual disease in breast and nodes must be strongly considered after an induction chemotherapy so as to choose adjuvant treatment for the individual patient.Prognostic factors are used to help clinical decision-making in selecting the appropriate treatment for individual patients. The purpose of this retrospective study was to identify one or more factors associated with overall survival (OS) and disease-free survival (DFS), in 710 patients with operable breast cancer, subjected to neoadjuvant chemotherapy followed by surgery, radiotherapy and adjuvant treatments. At a median follow-up of 7.6 years, univariate analysis showed that pathological complete response (pCR) was significantly related to survival (p< 0.003), as well as accepted prognostic factors, as SBR and MSBR grades, hormonal receptors or node involvement at surgery, who remained significant in our study (p< 0.001). The revised Nottingham prognostic index (NPI) and related indices (BGI, MNPI and MBGI) were also significantly associated to survival (p< 0.003). In multivariate analysis, node involvement and MSBR grade remained prognostic factors for OS and DFS (p< 0.0003 and p< 0.02, respectively). The MNPI and pCR were significantly related with OS (p= 0.04) and pts with hormonal receptor-positive tumours had a better DFS than others (p= 0.004). Among all clinical and pathological parameters, axillary dissection after neoadjuvant chemotherapy is still important to determine node involvement, a major prognostic factor. Moreover, MSBR grade seemed to be more accurate and predictive of long-term outcome than the standard SBR grade. It is concluded that, outside any other ‘biological’ factor, residual disease in breast and nodes must be strongly considered after an induction chemotherapy so as to choose adjuvant treatment for the individual patient.

Objective. To distinguish various types of local recurrence after conserving treatment of breast cancer and to evaluate their predictive value. Materials and methods. We first researched the pronostic factors after local recurrence and second evaluated the predictive factors of skin and inflammatory recurrences out of a series of 605 cases of stage I and stage II breast cancer of less than 4cm in diameter that occurred after conserving treatment. Results. Multivariate analysis revealed two major predictors of poor prognosis associated with recurrence: early appearance Hazard ratio 3.0 (1.28–7.00) (p=0.011) and inflammatory or skin involvement Hazard ratio 3.38 (1.36–8.45) (p=0.009). A local recurrence multiplied the relative risk for metastasis by 2.6. This result depended on the type of recurrence: when those with inflammatory and cutaneous types were excluded, local recurrence was no longer a poor prognostic factor. Patients who experienced primary invasive tumor with histologic multifocality have a 4.08 (1.44–11.59) (p<0.004) times greater risk of developing cutaneous or inflammatory recurrences compared with patients who experienced breast cancer unique localization. Conclusion. As histologic multifocality is the only factor predictive of dark prognosis local breast cancer recurrences, aggressive therapy at the time of the primary treatment could be the therapeutic implications of such finding on the original tumor.

Background.Obesity or increased body mass index (BMI) has been shown to have two important adverse effects related to breast cancer. First, several studies have identified an association between increased BMI and advanced stage breast cancer. Second, increased BMI has been shown to be associated with poorer prognosis. In a previous report, we had identified low BMI as a risk factor for local reccurence at five years. The objectives of this study were to evaluate the relationship between BMI and local control and to confirm this prognostic factor in a larger population with an important follow-up. Materials and methods.Between 1976 and 1988, 605 women with invasive breast carcinoma less than 4 cm in diameter underwent conservative surgery with axillary dissection and radiation therapy. The median follow-up time was 82 months. The risk of local recurrence and distant metastasis was evaluated by univariate retrospective analysis using Kaplan–Meier method for the main clinical and histologic factors. Those found to be significant were entered in a Cox model for multivariate analysis. Results.Since the beginning of the study, 80 patients had developed local recurrence. The 5 years and 10 years local control rates were 91 % and 83 %, respectively. Four parameters were independent predictive factors of local recurrence: Age lower than 40 years (HR = 2.42 95 % CI = [1.35–4.34]), BMI: elevation of one unit reducing the local recurrence of 0.92 95 %CI = [0.85–0.99], multifocality of the tumor on pathological examination (HR = 2.12 95 % CI = [1.16–3.88]) and positive axillary nodes HR = 0.54 95 % CI = [0.31–0.95]. Size of the breast was not a predictive factor for local cancer recurrence. Low BMI did not increase risk of distant. Conclusion.Our study offers new data concerning the possibility that thinness may be related to local recurrence of breast cancer.

Among the methodological approaches of tumor proliferation, thymidine kinase (TK) and thymidylate synthase (TS) assays take into account the specific pathways of pyrimidine synthesis. Studies pointing to a prognostic value of TK and TS in breast cancer involved small numbers of patients. We investigated the prognostic value of these enzymes and their combination in a large retrospective multicenter study. Nine hundred eight T1T2, N0N1, M0 primary breast cancer samples (median follow-up 68 months) were tested. TK and TS were measured in cytosols by using standardized radioenzymatic methods. Although a positive correlation was obtained between TK and TS (p&lt;10⁻⁵), major discrepancies were observed in some tumors. High levels of both enzymes were associated with large tumor size, histological grade III and steroid receptor-negative tumors. Univariate analysis showed that TK, TS and their combination were predictive of poor metastasis-free (MFS) (p &lt; 10⁻⁴; p=0.004; p &lt; 10⁻⁴) and disease-free survival (DFS) (p &lt; 10⁻⁴; p=0.007; p=0.0001). TK was selected as an independent factor for MFS in Cox analysis. It was the only variable selected in node-negative patients. Subgroups with specific outcomes, with possible therapeutic implications, were identified: a) in node-negative patients not receiving adjuvant treatment, TK values in the 4th quartile were associated with poor MFS (p=0.0002) and DFS (p=0.0005) as compared to the other quartiles; b) in node-positive patients receiving adjuvant chemotherapy, low levels of both TK and TS were associated with the highest survival rates (MFS: p=0.04; DFS: p=0.03). Int. J. Cancer 87:860–868, 2000. © 2000 Wiley-Liss, Inc.

In a previous pilot study, we showed that polyunsaturated n-3 fatty acids of breast adipose tissues were associated with breast cancer multifocality. In the present study, we investigated biochemical, clinical and histological factors associated with breast cancer focality in a large cohort of women with positive hormone-receptors tumors.

Between 1976 and 1986, we treated 115 patients (mean age 53.8 years) with base of tongue carcinomas. The staging system used was the UICC TNM classification of 1979. Seventy per cent of the tumours were T3 or T4 and 42% had N2 or N3 lymph nodes. Locoregional treatment was irradiation alone (98/115) or surgery and post-operative radiotherapy (17/115). Sixtyseven patients received induction chemotherapy. Actuarial survival of the entire group at 3 and 5 years was 25 and 23%, respectively, and 3-year actuarial survival rates for Tl, T2, T3 and T4 lesions were 42, 48, 20 and 17%, respectively. The local control rate at the primary site was 55% and 78% in the neck. Distant metastases occurred in 10% of patients and 8% had a second primary. Nodal status was the only other prognostic factor. The local control rate obtained with irradiation alone was not good. For limited Tl and T2 tumours, interstitial therapy or surgery should improve the local control rate.