Organized breast screening: Answers to recurring controversies.

The reduction in mortality specifically from breast cancer, demonstrated in the major meta-analyses in the 1980s resulted in public health breast cancer screening programs being set up in many countries, including France. Recent publications have challenged the usefulness of screening, by insisting in particular on the negative effects of overdiagnosis and the lack of any significant impact on mortality. From analysis of the literature and particularly independent reviews published in 2012, we provide some answers for doctors faced with the legitimate concerns of women. These studies confirm that screening in the right age group reduces specific mortality by at least 20% at a cost of overdiagnosis estimated at between 1 and 15%.

[What do clinicians do with the results of the systematic staging imaging at the time of the breast cancer diagnosis?]. / Bilan d'extension des cancers du sein: résultats et conséquences cliniques.

INTRODUCTION: Asymptomatic distant metastasis is often looked for at the time of initial diagnosis of early breast cancer. However, there is no consensus on when to perform it and on the consequences on the treatment. PATIENTS AND METHODS: One hundred and twenty-three asymptomatic women receiving systemic neoadjuvant (32 patients) or adjuvant treatment (91 patients) for breast cancer at the Oscar-Lambret center in September 2011 were considered. The staging imaging was a PET scan for 59 patients (pts), a CT scan and a bone scan for 59 patients and both for 5 patients. The result for each procedure was considered normal, abnormal but typically benign or potentially malignant. In this case, another imaging technique was carried out to confirm the suspected diagnosis. The patient was considered metastatic if the results of two different procedures were concordant and eventually in case of response to chemotherapy. RESULTS: Nine pts were considered metastatic (9/125=7%). They were stage 1: 1, stage 2: 4 and stage 3: 4. The staging by CT, abdomen and pelvis scan coupled with bone scintigraphy discriminated five metastatic patients with overdiagnosis of 33 benign lesions and the need of 20 additional confirmatory tests. Similarly, the PET staging, more expensive, only discriminated two metastatic patients and 15 benign lesions requiring 20 confirmatory tests. CONCLUSION: These results support the international recommendations to make a staging from stage IIIA. The CT, abdominal and pelvic scan coupled with bone scintigraphy should be considered as a gold standard in breast cancer staging.

A retrospective case series of 103 consecutive patients with leptomeningeal metastasis and breast cancer.

Approximately 2-5 % of patients with breast cancer (BC) develop leptomeningeal metastasis (LM). 103 consecutive patients with BC were diagnosed with LM and initially treated with intra-CSF liposomal cytarabine from 2007 to 2011 at a single institution. Correlations were determined with respect to patient characteristics and BC subtype with regard to overall survival (OS). At LM diagnosis, 61 % of patients had a 0-2 performance status (PS), the remaining 39 % were severely neurologically impaired. Regardless of PS, all patients received intra-cerebrospinal fluid (CSF) liposomal cytarabine as first-line treatment. Systemic treatment and radiotherapy were also given in 58 and 17 % of patients respectively as clinically appropriate. Second- (intra-CSF thiotepa) and third-line (intra-CSF methotrexate) treatment was administered in 24 and 6 patients respectively. Median OS was 3.8 months (range 1 day-2.8 years). In multivariate analysis, an initial combined treatment, a second-line treatment with intra-CSF thiotepa, an initial clinical response, and a non-'ER/PR/HER2 negative' BC were significantly associated with a better OS. Median OS in this heterogeneous retrospective case series was similar to that of previously observed BC patients treated with intra-CSF methotrexate suggesting intra-CSF liposomal cytarabine is a reasonable first choice therapy of BC-related LM.

[Role of MRI in the presurgical work-up of breast cancer: appropriate utilization of MRI as a complement to mammography and ultrasound]. / Place de l'IRM dans le bilan préchirurgical du cancer du sein: pour une utilisation raisonnée de cet examen complémentaire du bilan mammo-échographique.

The role of MRI for presurgical local staging of breast cancers amenable to conservative treatment has been the subject of multiple publications and tends to become a "validated" indication in routine practice. The purpose of the paper is to review the advantages and limitations of this imaging modality that is part of a comprehensive management that must be validated by clinical data especially with regards to local recurrence and survival. Knowledge of these elements combined with more precise indications should result in improved patient management while avoiding overtreatment or unnecessary anxiety-producing examinations.

[Follow-up of patients treated for localized invasive breast carcinoma]. / Surveillance après traitement des cancers du sein localisés invasifs.

The follow-up of patients treated for invasive breast carcinoma remains a major challenge because of breast cancer prevalence and the frequent patient's preferences for a regular follow-up. Concerning this last point, there is a lack of studies about the consequences of a systematic follow-up. Few decades ago, regular and systematic follow-up was considered as a dogma. In 1994, it was seriously questioned by two randomised Italian trials: they did not find any benefit in terms of survival and quality of life in patients who had a regular search of asymptomatic metastasis. Follow-up strategy after early breast cancer is still an unexplored field, despite higher performance of investigation tests and development of new treatments strategies that allowed a significant decrease of recurrences and increase of cancer care. Currently, the international guidelines deeply recommend a regular physical examination and mammography. But a systematic search for non-symptomatic metastases is unnecessary. We now need a coordination between practitioners to avoid useless tests, and to respond to patients' will.

[Evidence-based medicine: towards evidence-based radiology]. / "Evidence-based" medicine: vers une imagerie basée sur les preuves.

PURPOSE: To present evidence-based medicine (EBM), a concept that has been emerging over the decade, and to propose a reflexion about the role of radiologists in this new paradigm of medical practice. Clinical decision making. This new paradigm proposes the use of the best evidence and patient's participation in making medical decisions with de-emphasizing of intuition and empirical medicine. Application to a practice policy. EBM imposes new skills for physicians: clinical practice guideline is a witness of its importance. The main objective of EBM is to assist practitioners in their decision making process, but limits of this new concept must be known when it is used to control health-care resources or practice policies. Towards evidence-based radiology. What is the place for radiologists (diagnosis or interventional) in this new very popular paradigm?

[Patient choice for cancer treatment: towards a shared-decision model?]. / In process citation

The process of medical decision implies the elaboration of a choice between alternatives. Who has the choice? The doctor? The patient? Both? That depends on the particular characteristics of the patient and of the tumour, but also of the characteristics of the doctor and of his approach of medical discipline. For that reason, we planned first to remind some principles. In our analysis, the patient-doctor's relationship ties with environment, culture and habits. Philosophical principles, moral, and models of the relation between patient and doctor concern first part. In the second part, these ideas are compared with our routine practice: surveys about patients' needs, the obstacles for complete information and participation, studies on patients' preferences. The authors' analysis is that we are going inescapably towards shared decision-making taking into account the patients preferences. This evolution is not only tied with ethical principles, but with medical reason, i.e. the variability of patients' preferences led to tailor the treatment to the individual patient especially when benefit is limited. Of course, the applicability of a shared model depends on the particular situation of the patient and of his demand. It is all the easier as the consequences of the treatment are well known the riks tiny and distant. In the classical paternalistic model, there is no choice for the patient because the doctor(s) give the treatment. In the ideal model of the shared decision, doctor and patient progress together towards medical decision, in this case, the patient is not alone facing a choice, and in all cases, he is never alone.

Clinical evidence for topotecan-paclitaxel non--cross-resistance in ovarian cancer.

PURPOSE: A large, randomized study comparing the efficacy and safety of topotecan versus paclitaxel in patients with relapsed epithelial ovarian cancer showed that these two compounds have similar activity. In this study, a number of patients crossed over to the alternative drug as third-line therapy, ie, from paclitaxel to topotecan and vice versa. We therefore were able to assess the degree of non-cross-resistance between these two compounds. PATIENTS AND METHODS: Patients who had progressed after one platinum-based regimen were randomized to either topotecan (1.5 mg/m(2)/d) x 5 every 21 days (n = 112) or paclitaxel (175 mg/m(2) over 3 hours) every 21 days (n = 114). A total of 110 patients received cross-over therapy with the alternative drug (61 topotecan, 49 paclitaxel) as third-line therapy. RESULTS: Response rates to third-line cross-over therapy were 13.1% (8 of 61 topotecan) and 10.2% (5 of 49 paclitaxel; P =.638). Seven patients who responded to third-line topotecan and four patients who responded to paclitaxel had failed to respond to their second-line treatment. Median time to progression (from the start of third-line therapy) was 9 weeks in both groups, and median survival was 40 and 48 weeks for patients who were receiving topotecan or paclitaxel, respectively. The principal toxicity was myelosuppression; grade 4 neutropenia was more frequent with topotecan (81.4% of patients) than with paclitaxel (22.9% of patients). CONCLUSION: Topotecan and paclitaxel have similar activity as second-line therapies with regard to response rates and progression-free and overall survival. We demonstrated that the two drugs have a degree of non-cross-resistance. Thus, there is a good rationale for incorporating these drugs into future first-line regimens.

Comparison of physicians' and cancer prone women's attitudes about breast/ovarian prophylactic surgery. Results from two national surveys.

Prophylactic surgery is a major issue for breast/ovarian cancer prone women. Bio-clinical data to help in the decision-making are not sufficient. In this context of uncertainty, physicians' and women's attitudes to prophylactic surgery is information of great value. The physicians' attitudes were assessed by a randomised national sample of practitioners involved in breast and ovarian cancer management. The patients' attitudes were appraised with a pre-consultation self- administered questionnaire presented during a one-year period to all women in five cancer genetic clinics chosen, for their representative geographical locations and their activity level. Consent to prophylactic surgery is higher among physicians than among patients (p < 0.0001). Acceptability of mastectomy is lower than that of oophorectomy in both patients and physicians (p < 0.0001 in both groups). In addition, age at which the intervention is proposed to be performed is a key determinant for both mastectomy and oophorectomy acceptability, in both physicians and patients (p < 0.001 for each comparison). Particularly, the age of 40 years seems to be a critical threshold for the acceptability of prophylactic oophorectomy. In contrast, respondents' age at the time of the survey has no significant effect on the acceptability rate. The higher acceptability rate of prophylactic oophorectomy compared to that of mastectomy observed in the physicians' survey is paradoxical because a more substantial medical impact on life expectancy was expected from the latter. Our results indicate that assumed reduced mortality is not the main criterion steering acceptability. It was anticipated that prophylactic mastectomy should be rarely performed in France.

Multicenter phase II-III study of oxaliplatin plus cyclophosphamide vs. cisplatin plus cyclophosphamide in chemonaive advanced ovarian cancer patients.

PURPOSE: A phase II-III randomised study to compare safety and efficacy of an oxaliplatin/cyclophosphamide (OXAC) combination, vs. the reference combination of cisplatin/cyclophosphamide (CPC), in untreated advanced ovarian cancer patients. PATIENTS AND METHODS: 182 patients were enrolled, of whom 177 were treated: 86 with OXAC (130 mg/m2 oxaliplatin two-hour intravenous (i.v.) infusion, 1,000 mg/m2 cyclophosphamide two-hour i.v. infusion), and 91 with CPC (100 mg/m2 cisplatin one-hour i.v. infusion. 1,000 mg/m2 cyclophosphamide two-hour i.v. infusion). Treatment cycles were repeated every three weeks (maximum of six cycles). RESULTS: The main toxicities, which were significantly less severe in the OXAC arm, were myelosuppression and vomiting, including (OXAC vs CPC, % patients): grade 3-4 leukopenia (37% vs. 56%), and anaemia (7% vs. 32%), with blood transfusions in 8% vs. 21%. In the OXAC arm, 64% of surgically assessable patients and 33% of clinically assessable patients achieved an objective response. In the CPC arm, 67% patients achieved a surgical response and 42% achieved an objective clinical response. In the OXAC and CPC arms, median progression free-survival was 13.0 and 13.3 months, and overall survival was 36.0 and 25.1 months respectively, without statistically significant difference. CONCLUSION: The activity and time-related parameters of the OXAC and CPC combinations in advanced ovarian cancer patients, are comparable. Combined with the better safety profile of the oxaliplatin-containing regimen, this confirms the interest of oxaliplatin combined with active new agents in this indication.

[Predictive value of abdominopelvic scan for optimal surgery of ovarian carcinoma]. / Travail original présenté lors de la Société Françaiseurgie d'oncologie Gynécologique des 5 et 6 novembre 1999. Valeur prédictive du scanner abdomino-pelvien pour la chirurgie optimale des carcinomes de l'ovaire.

BACKGROUND: Some patients undergo laparoscopy without optimal debulking surgery as initial treatment for advanced ovarian carcinoma. The amount of residual tumor following primary surgery is an important prognosis factor. Neoadjuvant chemotherapy is a new therapeutic approach. Secondary, optimal surgery could be done in better conditions. PURPOSE: To access the ability of preoperative abdominopelvic CT to predict success of debulking surgery for ovarian carcinoma: less than 1cm of residual tumor size after initial surgery. MATERIALS AND METHODS: We reviewed 39 patients (two stage Ic, 1 stage IIc, 22 stage III and 14 stage IV) operated on for ovarian carcinoma between January 1992 and December 1997. Surgical criteria of inability to perform optimal surgical cytoreduction were compared with abdominopelvic CT done the month before. CT scans were prospectively assessed by radiologist A and retrospectively (3 months to 6 years delay) reviewed separately by radiologists A and B without surgical data. RESULTS: Nineteen patients underwent optimal debulking surgery: 13 no residual tumor and 6 with residual lesions under 1cm. The interreader (0.73) and intrareader (0.9) agreement, worked out by Kappa coefficient, was judged good to very good. The sensitivity of CT was 91% with a specificity of 95%. CONCLUSION: These results allowed us to determine which CT criteria were accurate and reproducible to be a helpful for therapeutic choice and to avoid laparotomy without optimal surgery.

Tamoxifen adjuvant treatment duration in early breast cancer: initial results of a randomized study comparing short-term treatment with long-term treatment. Fédération Nationale des Centres de Lutte Contre le Cancer Breast Group.

PURPOSE: In 1986, The Fédération Nationale desCentres de Lutte Contre le Cancer Breast Group initiated a multicenter randomized trial to assess the usefulness of long-term adjuvant tamoxifen treatment. Short-term adjuvant tamoxifen treatment was to be compared with life long adjuvant tamoxifen treatment. PATIENTS AND METHODS: Patients who were disease-free after 2 to 3 years of adjuvant tamoxifen treatment were eligible for the trial. From September 1986 to May 1995, 3,793 patients were randomized from France, Belgium, and Argentina. A total of 1,882 patients stopped tamoxifen (short-term group), and 1,911 patients were to continue tamoxifen for life (long-term group) at the same dose as previously prescribed. The protocol was modified in February 1997, limiting tamoxifen treatment to 10 years after randomization, thus giving a comparison between a 2- to 3-year treatment and a 12- to 13-year treatment. To date, the median duration of tamoxifen treatment is 30 months in the short-term group, and 70 months in the long-term group. RESULTS: Overall, longer tamoxifen treatment induced a 23% reduction in relapse rates, leading to a 7-year disease-free survival rate of 78%, compared with 72% in the shorter-treatment group. In contrast, overall survival did not differ between the two groups, with a 79% overall survival rate in both groups. This improvement in disease-free survival could be observed in node-positive patients (P: =.001); however, it was not found in node-negative patients. Prolonged tamoxifen treatment corresponded to a significant increase in disease-free survival in estrogen receptor-positive patients (P: =.03) as well as in estrogen receptor-negative patients (P: =.05). Furthermore, longer treatment reduced contralateral breast cancers and did not increase the number of endometrial cancers. CONCLUSION: Although no survival advantage was noted, patients did benefit from longer tamoxifen treatment over 3 years and had significantly better disease-free survival compared with patients who stopped hormonal treatment. Long-term follow-up is needed to assess these results. Most patients in the long-term group are still receiving treatment. Comparison of results as time passes will enable conclusions to be made on the value of long-term treatment over 5 years compared with 2 to 3 years.

Evaluation of toxicity and efficacy of 186Re-hydroxyethylidene diphosphonate in patients with painful bone metastases of prostate or breast cancer.

UNLABELLED: Twenty-eight patients (12 men with prostate cancer, 16 women with breast cancer) were included in a phase II trial to evaluate the efficacy of 186Re-hydroxyethylidene diphosphonate (HEDP) on pain from bone metastasis and the toxicity of this agent. METHODS: After intravenous administration of 1295 MBq 186Re-HEDP, the efficacy was evaluated by means of a daily log. RESULTS: We observed an objective response in 67% of prostate cancer patients and in 36% of breast cancer patients. The mean duration of response was 45 d for prostate cancer patients and 24 d for breast cancer patients. No major adverse effects were observed. Marrow toxicity did not exceed grade 2 for white blood cells and grade 3 for platelets using National Cancer Institute criteria. CONCLUSION: 186Re-HEDP provides safe symptomatic relief of pain in prostate cancer patients. The benefit of this treatment is less clear in breast cancer patients. Further studies should be conducted to evaluate treatment by 186Re-HEDP at an earlier stage of the disease.

Disclosure to the family of breast/ovarian cancer genetic test results: patient's willingness and associated factors.

Informed probands are key actors for disclosing genetic information to their relatives when a mutation has been identified in the family. The objectives were to study women's attitudes towards the family disclosure of positive breast cancer genetic testing results and to determine the predictive factors of the diffusion patterns observed. A national multi-center cross-sectional survey was carried out at five French cancer genetic clinics during a 1-year period. Self-administered questionnaires were completed after the consultation by 84.5% (398/471) of women attending breast cancer genetic clinics for the first time. Among the 383 respondents who had at least one living first-degree relative to inform, 8.6% would inform none, 33.2% would inform at least one of them, and 58.2% would inform all of them. The sibship would be the most frequently informed blood relatives, sisters in 86.9% and brothers in 79% compared with mother in 71.4%, children in 70.4%, and father in 64.9%. Women of the family would be more frequently informed than men (P < 0.05). After multivariate adjustment, age, the fact to be affected by cancer, the number of daughters, and the emotional disturbance due to cancer in a close relationship were the main determinants (P < 0.05) of the diffusion patterns observed. The first step of the relatives' attendance to genetic counseling and the proband's willingness to disclose breast cancer genetic tests results was high in this study and was clearly dependent on the women's personal and emotional characteristics.

Surgical staging of early invasive epithelial ovarian tumors.

Early stage epithelial ovarian carcinoma is defined pathologically as a tumor strictly limited to one or both ovaries without any extra-ovarian disease (i.e., Stage IA or B of the International Federation of Gynecology and Obstetrics (FIGO) classification). This diagnosis can be obtained only after an exhaustive surgical staging procedure, performed as soon as the diagnosis of epithelial invasive ovarian carcinoma is established. This staging surgery currently encompasses a peritoneal cytology, the thorough inspection of all the visceral and parietal peritoneal surfaces with biopsy of any abnormality, total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH + BSO), random peritoneal biopsies, omentectomy, appendectomy and bilateral pelvic and para-aortic lymphadenectomies, up to the left renal vein. The results of this staging procedure and its indications are discussed. In all of the cases, the radical removal of the pathologic adnexa is indicated, along with the complete peritoneal and retroperitoneal staging. While fertility-sparing surgery (avoiding hysterectomy and contralateral adnexectomy, if possible) seems to be safe for young women, a TAH + BSO is the rule for the others. Adjuvant chemotherapy can be omitted in well-differentiated tumors with a negative staging operation, but currently it remains indicated in all other cases. Indeed, the ultimate goal in early stage ovarian carcinoma is to not impair by inadequate management the high chance of a cure.