[Patients' preferences and decision-making: state of the art and applications in cancer]. / Préférences des patients et prise de décision : état des lieux et retour d'expérience en cancérologie.

BACKGROUND: This paper deals with the physician-patient encounter. In France, the current legal framework allows patients to be informed (patients' rights to health information) and to participate to decisions regarding their own health. In such a context, this paper aims to give the reader the broad key components of the so-called 'patient treatment preferences elicitation process' in breast cancer, our research area. METHODS AND RESULTS: We first present the general context, with a definition of the different physician-patient models. We then present decision aids, tools that aim to provide high-quality information to patients in the decision-making process. Finally, based on our previous studies and on examples drawn from the international literature, we present the empirical process of patients' preferences elicitation, which not only increases patients' knowledge of and satisfaction with the decision made, but also allows patients to be part of their disease management. CONCLUSION: Far from being a phenomenon in the air supported by a legal system, this method developed in the 90s allows patients and more generally healthcare users to be autonomous without constraining them to a choice.

[Oncoplastic technics with nipple-areolar complex resection for the treatment of central breast cancers]. / Chirurgie oncoplastique pour le traitement des tumeurs mammaires centrales.

Central breast cancer has long been an indication for mastectomy. Plastic surgical techniques adapted to cancer (oncoplastic surgery) have made it possible to offer breast cancer patients conservative surgery with resection of the nipple-areolar complex (NAC). We evaluated carcinologic results and cosmetic outcomes as a function of the oncoplastic technique used. We performed a retrospective study in 47 patients with central breast cancers undergoing breast-conserving with NAC resection. Carcinologic results were assessed by calculating local and metastatic recurrences rates. Cosmetic results were evaluated on four criteria assessed by the patient then by two surgeons. The mean age of the patients was 59.8 (44-84) years. The mean tumour diameter was 17.4 (6-39)mm. Histological involvement of the nipple is present in 53% of the cases. No local recurrence, neither death was observed at 4.5 years median follow-up. One patient had liver metastatic recurrence at 83 months. Cosmetic results were assessed in 33 patients. Round-block provided better aesthetic results: the shape of the breast was considered very good or satisfactory for 90% of the surgeons with the round-block technique and for 46% with transverse incision (P=0.02). Breast-conserving surgery is feasible in selected patients with T1 or T2 central breast cancers, with no impact on the risk of local recurrence. NAC resection is essential especially when the patients have clinical signs of nipple involvement. It provides satisfactory cosmetic results, especially with the round-block technique, possibly associated with nipple reconstruction using the "cat-design" technique developed by our team.

Prognostic value of P53 gene mutations in a large series of node-negative breast cancer patients.

The most important subgroup of breast cancer patients for which reliable prognostic factors are needed are women without axillary lymph node involvement. Although overall, these patients have a good prognosis, it is known that 20-30% will experience a recurrence of the disease. To determine the prognostic significance of P53 tumor suppressor gene mutation, specimens from 113 primary breast cancers were evaluated for the presence of P53 alterations, as detected by cDNA sequencing of the entire coding sequence of the gene. The median follow-up for patients was 105 months. P53 gene mutation was an independent prognostic marker of early relapse and death. Our results suggest that P53 gene mutations could be an important factor to identify node-negative patients who have a poor prognosis in the absence of adjuvant therapy. Prospective studies should be designed to determine which therapy should be performed in this subgroup of patients.

Tubulin detyrosination is a frequent occurrence in breast cancers of poor prognosis.

Tubulin, the dimeric subunit of microtubules, is a major cell protein that is centrally involved in cell division. Tubulin is subject to specific enzymatic posttranslational modifications including cyclic tyrosine removal and addition at the COOH terminus of the alpha-subunit. Tubulin is normally extensively tyrosinated in cycling cells. However, we have previously shown that detyrosinated tubulin accumulates in cancer cells during tumor progression in nude mice. Tubulin detyrosination, resulting from suppression of tubulin tyrosine ligase and the resulting unbalanced activity of tubulin-carboxypeptidase, apparently represents a strong selective advantage for cancer cells. We have now analyzed the occurrence and significance of tubulin detyrosination in human breast tumors. We studied a total of 134 breast cancer tumors from patients with or without known complications over a follow-up period of 31 +/- 10 months. The mean age of the patients at the time of diagnosis was 57 years. For each patient, detailed data concerning the histology and extension of the tumor were available. Tumor cells containing detyrosinated tubulin were visualized by immunohistochemical staining of paraffin-embedded tissue sections. Cancer cells with detyrosinated tubulin were observed in 53% of the tumors and were predominant in 19.4% of the tumors. Tubulin detyrosination correlated to a high degree of significance (P < 0.001) with a high Scarf-Bloom-Richardson (SBR) grade, a known marker of tumor aggressiveness. Among SBR grade 1 tumors, 3.8% were strongly positive for tubulin detyrosination compared with 65.4% of the SBR grade 3 tumors. The SBR component showing the strongest correlation with tubulin detyrosination was the mitotic score. In the entire patient population, neither the SBR grade nor the detyrosination index had significant prognostic value (P = 0.11, P = 0.27, respectively), whereas a combined index was significantly correlated with the clinical outcome (P = 0.02). A preliminary subgroup analysis indicated that tubulin detyrosination may define high- and low- risk groups in breast cancer tumors with an SBR grade of 2. Our study shows that tubulin detyrosination is a frequent occurrence in breast cancer, easy to detect, and linked to tumor aggressiveness.

Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: a double-blind, placebo-controlled study.

PURPOSE: To determine the effectiveness and safety of the bisphosphonate risedronate in preventing bone loss in young women with breast cancer and early menopause induced by chemotherapy who are at major risk for the development of postmenopausal osteoporosis. PATIENTS AND METHODS: Fifty-three white women, aged 36 to 55 years, with breast cancer and artificially induced menopause were stratified according to prior tamoxifen use. Thirty-six patients received tamoxifen (20 mg/d). Within each stratum, patients were randomly assigned to receive risedronate (n = 27) or placebo (n = 26). Treatment consisted of eight cycles oral risedronate 30 mg/d or placebo daily for 2 weeks followed by 10 weeks of no drug (12 weeks per cycle). Patients were monitored for a third year without treatment. RESULTS: Main outcomes of the study were changes in lumbar spine and proximal femur (femoral neck, trochanter, and Ward's triangle) bone mineral density (BMD), and biochemical markers of bone turnover. In contrast to a significant decrease of BMD at the lumbar spine and hip in the placebo group, there was an increase in BMD in the risedronate group. On treatment withdrawal, bone loss ensued, which suggests that treatment needs to be continuous to maintain a protective effect on bone mass. At 2 years, the mean difference (+/- SEM) between groups was 2.5% +/- 1.2%, (95% confidence interval [CI], 0.2 to 4.9) at the lumbar spine (P = .041) and 2.6% +/- 1.1%, (95% CI, 0.3 to 4.8) at the femoral neck (P = .029). Similar results were observed at the hip trochanter. Results by stratum indicate a beneficial, although partial, effect of tamoxifen in reducing bone loss. Risedronate was well tolerated and showed a good safety profile, with no evidence of laboratory abnormalities. CONCLUSION: Risedronate appears to be a safe treatment that prevents both trabecular and cortical bone loss in women with menopause induced by chemotherapy for breast cancer.

Abnormal expression of the ATM and TP53 genes in sporadic breast carcinomas.

The ataxia telangiectasia gene (ATM) has been implicated as a risk factor in the development of sporadic breast carcinomas. ATM protein expression was analyzed by immunohistochemistry in 17 breast carcinomas with two monoclonal antibodies whose immunohistochemical use was first validated by comparing the immunoreactivity observed in spleen samples from ataxia telangiectasia and trauma patients. In normal breast ducts, ATM showed nuclear expression in the epithelial but not in the myoepithelial cells. In contrast, this nuclear expression was absent or low in the epithelial cancer cells in 10 of 17 (59%) of the tumors studied. Allelic imbalance in the ATM gene was found in three of seven tumors examined. Two of these showed reduced ATM protein expression, but this did not correlate with the presence of ATM mutations in the tumor DNA detected by restriction endonuclease fingerprinting screening. These results suggest that the reduced ATM protein expression could be attributable, in certain tumors, to deletions or rearrangements within or close to the ATM gene. Positive p53 immunostaining was found in 10 tumors, with TP53 mutations detected in 8. Three tumors had both low ATM expression and mutated TP53. Our results indicate that in the majority (15 of 17) of the sporadic breast carcinomas examined, not only is the functionality of the ATM-p53-mediated DNA damage response compromised, but also other signaling pathways activated by these two multifunctional proteins are likely to be impaired, which could be a contributing factor to tumor development and progression.

[Reattendance of women for breast cancer screening programs. A review]. / Participation secondaire des femmes au dépistage organisé du cancer du sein Revue de la littérature.

BACKGROUND: In France, breast cancer is the most frequently occurring cancer and the leading cause of cancer deaths in women. Breast cancer screening has been shown to reduce breast cancer mortality by 30% provided attendance rate is 70% and re-screening interval is two to three years. Maintaining a high rate of reattendance is also important. The decline with time of completion rates of re-screening will lessen the benefits of a breast cancer screening program. METHODS: A review of published studies examining factors associated with attendance and reattendance to breast cancer screening. RESULTS: Positive views about initial screening are determining factors in reattendance: mammography should not be painful and embarrassing, appointments should be punctual and clinic staff courteous and supportive. Psychological factors influencing attendance also influence reattendance as does intention to participate, a major predictor of repeat participation and as do perceived susceptibility of breast cancer, perceived benefits of mammography, absence of emotional barriers. These factors can be modified by experience of previous screening. Other predicting factors of attendance continue to influence reattendance: practice of other preventive health behaviors, outside support from physicians, knowledge of breast cancer and screening. CONCLUSION: A better understanding of factors influencing attendance is necessary to increase the impact of breast cancer screening. Field studies are necessary to support the elaboration of publicity campaigns aimed at increasing participation.

Association between breast cancer and family malignancies.

In a case-control study, the relationship between a family history of cancer of the breast, ovary, colon, uterus or prostate and the risk of breast cancer was investigated. The data consisted of family histories from 495 breast cancer cases and 785 controls aged 20-56 years. A positive association was found between the occurrence of breast cancer and a history of breast cancer in the families of the subjects affected. This relationship increased linearly with both the degree of kinship of the affected relatives and with their number. The risk of breast cancer associated with other types of cancer in the family was not significantly different from unity.

Reproductive factors and breast cancer risk. Effect of age at diagnosis.

The data from a French case-control study of 495 patients with breast cancer and 542 control subjects interviewed in five French public hospitals, were analyzed to assess the effect of reproductive factors (age at menarche, age at first full-term pregnancy, the time interval between these two ages, and parity) on the risk of breast cancer. Age at menarche, age at first full-term pregnancy, the time interval between these two ages, and parity appeared to have a limited influence on breast cancer risk. However, the relationship between these factors and the risk of breast cancer varied according to the age at breast cancer diagnosis. In the youngest group of women, the most consistent effects came from factors occurring early in life (menarche, first full-term pregnancy, and consequently the time interval between these two events). These factors had a null or weak effect on the oldest group of women. The protective effect of high parity was confined to the oldest group of women.

Langerhans cells and epithelial cell modifications in cervical intraepithelial neoplasia: correlation with human papillomavirus infection.

The study of a series of 18 cervical intraepithelial neoplasia (CIN) grade II and III was aimed at determining the distribution and phenotype of immunocompetent cells (Langerhans cells, T and NK cells) and the alteration in the expression of EGF receptors and beta 2-microglobulin in correlation with human papillomavirus (HPV) infection (viral antigen and DNA typing with biotinylated probes). These lesions were characterized by a reduced number of Langerhans cells and a dense infiltrate. HPV infection did not induce HLA-DR expression in the infected epithelial cells. We observed an enhanced expression of epidermal growth factor (EGF) receptors by epithelial cells and a reduced beta 2-microglobulin reactivity by both epithelial and immunocompetent cells. Most of CIN showed foci of infected cells. No significant differences were observed in immunological markers of CIN harboring benign HPV 6/11 DNA or oncogenic HPV 16/18 DNA. Viral antigen was not detected in these lesions. These changes in the epithelial cells of CIN and their microenvironment associated to the lack of HLA-DR expression in the infected cells hamper the squamous epithelial cells to function as antigen presenting cells. This may facilitate a decrease in the immunological surveillance and may contribute to the severity of such lesions.

Structure and composition of microcalcifications in benign and malignant lesions of the breast: study by light microscopy, transmission and scanning electron microscopy, microprobe analysis, and X-ray diffraction.

Microcalcifications previously located by radiography were extracted from 25 fresh specimens obtained from patients who had undergone tumorectomy or systematized mammary exeresis. Two principal types of microcalcifications were distinguished: Type I microcalcifications were amber in color and generally crystalline on scanning electron microscopy, with only one calcium peak on microprobe analysis; x-ray diffraction revealed that weddellite was involved. Type II microcalcifications were whitish, nonbirefringent under polarized light, and generally ovoid or fusiform, with two peaks, one calcium and the other phosphorus, on microprobe analysis; these microcalcifications were composed of calcium phosphate, the most characteristic form of which is hydroxyapatite, in the form of needles arranged in rosettes on transmission electron microscopy. Type I microcalcifications were observed in four of eight benign breast lesions, in two of three in situ lobular carcinomas, and in no intraductal adenocarcinomas or infiltrating carcinomas. Type II microcalcifications were present in all infiltrating carcinomas and intraductal adenocarcinomas; they were also found in benign lesions (four of eight) and even associated with type I microcalcifications in one in situ lobular carcinoma. There are, therefore, no "benign" or "malignant" microcalcifications; however, the presence of weddellite is a strong indication that a lesion is benign or, at most, an in situ lobular carcinoma.

Variations in the risk of breast cancer associated with a family history of breast cancer according to age at onset and reproductive factors.

In a case-control study of 495 breast cancer patients and 785 controls between 20 and 56 years of age, the risk of breast cancer associated with a family history of breast cancer was studied according to age and reproductive factors. The familial risk of breast cancer was not significantly modified by age at onset, age at menarche, number of children, age at first full-term pregnancy, menstrual cycle length or age at menopause. However, the familial risk significantly increased with the number of abortions (p < 0.05) and seemed to decrease after a natural menopause (p = 0.08). These results suggest that a familial predisposition to breast cancer exerts the same influence during the first six decades of life, except maybe when there are isolated or repeated events such as abortions or artificially imposed menopause, in which case the risk is apparently greater.

Oral contraceptives and breast cancer: a French case-control study.

The relationship between the risk of breast cancer and oral contraceptive use was investigated in a case-control study conducted in France between 1983 and 1987 in five public hospitals. Some 464 cases aged 25 to 56 years and 542 matched controls were interviewed about their history of the use of oral contraceptives (OC). Results are given for the entire population and for the subgroup of 358 and 379 premenopausal cases and controls. The multivariate relative risk estimate, for ever user, was 1.5 (p less than 0.01) in the whole group as well as in the premenopausal subgroup (p less than 0.02). However, there was no evidence that the effect varied appreciably according to duration of use, age at first use, use before first full-term pregnancy (FFTP) and time since first or last use. The risk was not altered for any particular brand of OC. We conclude that, because of the widespread attention given to the relationship between OC use and breast cancer, information bias might be responsible for part of the excess in risk observed among OC ever users.

PIP: The relationship between the risk of breast cancer and oral contraceptive (OC) use was investigated in a case-control study conducted in France between 1983-87 in 5 public hospitals. Some 464 cases ages 25-56 years and 542 matched controls were interviewed about their history of OC use. Results are provided for the entire population and for the subgroups of 358 and 379 premenopausal cases and controls. The multivariate relative risk estimate, for ever-use, was 1.5 (p0.01) in the entire group as well as in the premenopausal subgroup (p0.02). However, there was no evidence that the effect varied appreciably according to the duration of use, age at 1st use, use prior to 1st fullterm pregnancy, and time since 1st or last use. The risk was not altered for any particular OC brand. The authors conclude that because of the widespread attention given to the relationship between OC use and breast cancer, information bias might be responsible for a part of the excess of risk observed among OC ever-users.

Sexually transmitted diseases as major causes of ectopic pregnancy: results from a large case-control study in France.

OBJECTIVE: To evaluate the current impact of sexually transmitted diseases (STDs) and their consequences on the occurrence of ectopic pregnancy (EP). DESIGN: Case-control study. SETTING: Fifteen maternity hospitals in the Rhône-Alpes region, France. SUBJECTS: Six hundred twenty-four women with EP diagnosed from October 1988 to December 1991 and 1,247 controls who delivered liveborn children during the same period. MAIN OUTCOME MEASURES: Information on risk factors included behavioral, clinical, and serological indicators of STDs and other known risk factors of EP. RESULTS: Logistic regression identified several indicators of STDs as strong and independent risk factors for EP: previously treated STD without history of salpingitis; history of probably pelvic inflammatory disease (PID) and, especially, history of confirmed PID; previous STDs of the sexual partner; and Chlamydia trachomatis seropositivity. The adjusted attributable fractions of EP for previous symptomatic STDs, symptomatic STDs of the sexual partner, and C. trachomatis seropositivity were 20%, 3.5%, and 25.2%, respectively, giving a total of 43% of EP cases attributable to infectious factors. CONCLUSIONS: Our findings and previous epidemiological and biological evidence suggest that STD is a major cause of EP. The evidence is particularly strong in the case of C. trachomatis infection. An effective way of dramatically reducing the EP rate would be to prevent STD through education programs sensitizing young women to the complications of STD and public health measures promoting the use of protective methods such as condoms.

Axillary lymph-node dissection for positive sentinel nodes in breast cancer patients.

AIM: The aim was to identify a subset of breast cancer patient with positive sentinel nodes (SNs) for whom secondary axillary clearance would be unnecessary. METHODS: Between March 1999 and May 2001, 288 patients with T0-T2 breast cancer less than 3cm in diameter had SN detection either by a colorimetric method or using a combined technique. SNs were stained with haematoxylin and eosin (H&E). For all negative SNs, serial sections and immunochemistry (IHC) were performed. All patients with positive SNs underwent a complete axillary lymph node dissection. One hundred and twenty patients were SN positve. RESULTS: Non-sentinel node positivity (NSNP) was closely associated with the size of the tumour (14.3%, 54.1% and 51.8% for pT1a-b, pT1c and pT2 tumours respectively) and with the size of the SN metastasis: 15.9% IHC detected micrometastasis, 33.3% and 78.8% micro- and macrometastasis detected with H&E staining respectively. NSNP was found in 24.0% and 42.8% of patients with pT1c breast cancer and with micrometastasis detected by IHC and H&E staining. The node positivity rate reached 81.1% for pT1c lesions with macrometastasis in the SN. For the patients with pT2 breast cancer, these rates were 12.5% (IHC), 28.5% (H&E) 91.1% (macrometastasis). CONCLUSIONS: We are unable to isolate precisely a subset of patients for whom total axillary lymph node dissection would be unnecessary. A subset of 14 small tumours (<1cm diameter) demonstrated micrometastases in the SN without NSNP.

Psychosocial profile of women seeking breast reconstruction.

As opposed to studies focused on the role of reconstruction in the rehabilitation of cancer patients, the aim of this study is to define what kind of women undergo post-mastectomy reconstruction. The social, cultural and psychological variables influencing women in this choice were assessed using a questionnaire administered to 45 women who had breast reconstruction and 51 who did not. An univariate analysis shows significant differences between the two groups regarding age, education, socioeconomic status, leisure activities, sexual intercourse, information about breast reconstruction and fear of recurrence. These results show that social status is a deciding factor in a woman's access to information about reconstruction. If every women undergoing mastectomy is to be given the opportunity of plastic surgery, we think that information must be adapted to psychosocial profile.

[Problem of perception and denial of illness in women who had breast cancer]. / Problème de perception et déni de la maladie chez des patientes ayant eu un cancer du sein.

It has been noted that some patients demonstrate denial when they have a severe illness such as cancer. We observed this type of denial with respect to perception of illness by patients. We interviewed twenty women who had been treated for breast cancer for more than one year. During these interviews, every patient narrated the story of her illness as she remembered it. One year or more after treatment, four women denied the diagnostic which was given to them when the treatments started. These four women were the only ones who never perceived the first signs of the illness. They never saw or felt any change around their breasts, and they are among the five women for whom breast cancer was detected from a systematic mammography. In contrast the other women, who did not manifest such denial, detected themselves an anomaly or were alerted by their physician. Based upon these observations, we discuss the notion of denial when patients have no perception of the illness or its first signs of onset. We pose a question concerning the interest and usefulness of such research concerning the representational process of illness by patients.

[Motivations for breast reconstruction after mastectomy. A comparative study]. / Motivations des femmes pour la reconstruction mammaire après mastectomie. Etude comparative.

The aim of this study is to define the psychosocial profile and the motivations of women who seek post-mastectomy reconstruction. A questionnaire was administered to 45 women who had breast reconstruction several months after mastectomy and 51 who did not. Statistical analysis of data shows significant differences between the two groups regarding age, education, leisure activities, sexual intercourse and fear of recurrence. A qualitative analysis shows how women feel about reconstruction. The results suggest that information concerning reconstruction must be adapted to the psychosocial profile of women. Moreover, reconstruction must be considered by the surgeon as an essential stage of breast cancer treatment. In order to help women in their choice, they must give them appropriate information on the technique of breast reconstruction, on the risk of relapse and on the possibility of reimbursement of medical expenses.

[Thermography of the breast. Sensitivity, specificity and reproducibility]. / Thermographie mammaire. Sensibilité, spécificité et reproductibilité.

Thermography is a questionable method of diagnosis of breast diseases. In our study, we demonstrate that the low sensitivity and specificity is not related to the experience of the reader. One hundred thermograms were given to five different readers: three of them were thermographists, one was a gynecologist and the last one radiotherapist. Sixteen patients had a breast carcinoma, 18 had benign lesions. Seventy-two patients had no lesion at the time of diagnosis and 4 years after. The false negative and the false positive rates were not different according to the readers. The reproducibility, judged with the Kappa test, was poor. This study, in agreement with most of the previous studies, demonstrates that thermography must not be recommended neither for diagnosis nor for screening of breast diseases.

[Study with serial sectioning of 312 preclinical cancers of the uterine cervix. Indications for selective treatment (author's transl)]. / Etudes par coupes sériées de 312 cancers pré-cliniques du col utérin. Déductions thérapeutiques.

The authors have studied by step serial sectioning 312 cervix the most obtained by cold knife conization. They have studied too, the frequency of inadequate resection (i.e. non in sano conization) and clinically occult invasion according to the age of patients. Conization is adequate for the treatment of 70 per cent of women less than 30 years of age. But after 50 it is sufficient in only 22 per cent of the patients. Conization must be performed in most cases of grade III to V cervical smear (according to Papanicolaou's classification). The cervical cone must be studied by serial sectioning (every 500 microns). According to the result of this study the treatment must be selected : conization for in situ carcinoma resected in sano, simple hysterectomy for in situ carcinoma not resected in situ and Wertheim type operation for invasive carcinoma.