[Breast density: a major parameter to follow during hormone replacement therapy]. / Densité mammaire: un paramètre à surveiller lors de la prise d'un traitement hormonal de la ménopause.

Mammographic density is a risk factor for breast cancer and it reflects variations in the tissue composition of the breast. It is notably influenced by body mass index and by endogenous hormones as well as hormone replacement therapy (HRT). The pathways that are responsible for the increase in mammographic density following exposure to hormones and those that increase risk of breast cancer are probably not the same. Careful clinical and mammographic follow-up is appropriate in women undergoing HRT because an increase in density is not only a risk factor for breast cancer but it also reduces screening sensitivity. We present a case in which mammographic density decreased after menopause, then dramatically increased after HRT and finally, surgical biopsy allowed the diagnosis of an infiltrative breast carcinoma. We discuss appropriate HRT changes in case of increasing mammographic density.

[Pregnancy after infiltrative breast cancer treatment: experience of the CHRU of Strasbourg with literature review]. / Grossesse après cancer infiltrant du sein: expérience du CHRU de Strasbourg et revue de littérature.

OBJECTIVES: Identification of women who survived infiltrative breast cancer and subsequently conceived and determination of the rate of pregnancy, the time from diagnosis to pregnancy, the outcome of breast cancer and of subsequent pregnancies. PATIENTS AND METHODS: Women treated for breast cancer at the Gynaecology and Obstetrics Unit of the University Hospital of Strasbourg between 1993 and 2007 who subsequently conceived were prospectively registered and followed yearly. RESULTS: Twenty pregnancies subsequent to surgery for breast carcinoma were observed in 598 patients. This association accounted for 3.3% of the cases of infiltrative breast carcinoma in potentially fertile women under 45. Six pregnancies were observed less than two years after breast cancer diagnosis (four abortions and two live births) and 17 pregnancies occurred after two years (three abortions, three miscarriages, one extra-uterine pregnancy and 10 live births). Two patients who developed distant metastases after pregnancy (less than one year and more than five years after diagnosis respectively) died. One patient, whose pregnancy occurred three years after the diagnosis, is still alive with a lung cancer and brain metastases. One patient was treated for local breast cancer recurrence. The overall prognosis was good, 18 patients (90%) being alive with a mean follow-up of 105 (S.D. 43) months. DISCUSSION AND CONCLUSION: Pregnancy is more likely to occur in patients with a prolonged survival and no evidence of disease. Maternal prognosis is mainly related to initial stadification of breast cancer and not to its hormonodependence.

Comparison of early performance indicators for screening projects within the European Breast Cancer Network: 1989-2000.

In 1989 the European Breast Cancer Network (EBCN) was established by the first pilot projects for breast cancer screening, co-funded by the Europe Against Cancer programme. We report early performance indicators for these EBCN projects while taking into account their organizational setting. Out of 17 projects in the network, 10 projects from six European countries contributed aggregated data on number of invitations, screening examinations, and breast cancers detected over the period 1989-2000. Results were summarized separately for projects in centralized versus decentralized health care environments. The European Guidelines for quality assurance in mammography screening provided reference values for the performance indicators. The most prominent finding in this study was the higher participation rate in centralized versus decentralized projects (average participation in 1998: 74 versus 33%; P<0.001), whereas the invitation system and screening policy in these projects were similar. Detection rates and characteristics of cancers detected at initial and subsequent screening examinations showed no significant differences between centralized and decentralized projects. Even though early performance indicators for centralized versus decentralized projects were similar, the impact of breast screening on mortality from this disease at the population level will differ since the decentralized projects reach only part of the target population.

CD44 exon 6 expression as a possible early prognostic factor in primary node negative breast carcinoma.

Breast cancer is the most common female malignancy affecting approximately one woman in eight. Many attempts have been made to define markers which may have potential clinical applications in diagnosis as well as therapy. New isoforms of CD44 with alternative spliced exons have recently been described. We studied the expression of CD44 exon 6 using a semi-quantitative RT-PCR reaction on a panel of 25 normal breast specimens, 10 mammary fibroadenomas, eight cystic samples and 52 primary breast tumors. Significant correlation was found between CD44 exon 6 expression and the overall survival of the N-M-population, P = 0.032, (logrank test by Mantel's method). The same result was also observed for the disease-free survival, P = 0.000002 (logrank test by Mantel's method). CD44 exon 6 expression, as detected by our RT-PCR-based method, might be a useful prognostic indicator of metastasis in breast cancer. However, these preliminary results need to be confirmed by later retrospective and prospective studies on a larger number of patients.

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.

[Specific expression of human pS2 gene in breast cancer]. / Expression spécifique du gène humain pS2 dans les cancers du sein.

The hormone-dependence of some human breast cancers is well recognized. However, the molecular mechanisms responsible for the growth stimulation of these cancers by oestrogens are still poorly understood. With the hope of elucidating these mechanisms, we have recently cloned and studied the structure-function relationship of the human oestrogen and progestin receptors, and also undertaken a study aimed at characterizing genes whose expression is controlled by oestrogens in hormone-dependent breast cancers. We review here our findings concerning one of these genes and its expression products, the pS2 gene. We discuss also whether a systematic determination of pS2 gene expression in breast cancer biopsies could be useful to establish a new biochemical classification of these cancers which may be useful to improve the diagnosis of hormone-dependent cancers.

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.

Expression of CD44 spliced variants with both exons v9 and v10 in primary N(-)M(-) breast carcinomas correlates with metastasis.

We analyzed the representation of CD44 isoforms with both exons v9 and v10 among CD44 total amount and also examined correlation between their expression, clinical parameters and survival. We used a semi-quantitative RT-PCR reaction and a panel of 25 normal breast specimens, 10 mammary fibroadenomas, 8 cystic samples and 52 primary breast tumors. CD44 expression level was statistically higher in malignant tumors than in normal breast tissues (p = 0.038) or in fibroadenomas (p = 0.047) and correlated with histological grading, p = 0.047. Ratios CD44 variants with both exons v9 and v10/ total CD44 were similar in normal breast tissues and fibroadenomas but lower in the cystic samples. In primary N(-)M(-) breast tumors, unfavourable outcome and relapse were correlated with low ratios.

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.

Are CD44 spliced variants involved in human breast cancer metastasis?

Expression of CD44 isoforms has been investigated on normal breasts, fibroadenomas, cysts and breast cancers. Carcinomas express additional variants in comparison with normal breasts while fibroadenomas and cysts do not. Invasive cancers also express more variants than in situ carcinomas. Recent studies tend to demonstrate that overexpression of CD44 is not a survival prognostic factor whereas expression of exon 2v and/or 3v could be. Results for exons 4v to 10v are presently conflicting. Further studies will then be necessary to clarify the role of CD44 isoforms in mammary carcinogenesis and metastasis. Metastatic capacity could be linked with expression of additional variants but also with no transcription of variants associating exon 6v with either exon 10v or both exons 9 and 10v.

Quality control in mammography: an initiative in France.

The ultimate effectiveness of any mass screening campaign is directly related to strict compliance with certain rules and technical protocols designed for radiological installations. Concerning radiological screening, the primary technical objective is to ensure reproducibly high quality images at low radiation dose to the patient. This paper describes the methodology followed for the implementation of a quality control (QC) programme of 48 mammography installations used within the context of the breast cancer screening campaign in the Bas-Rhin region of eastern France. In order to demonstrate the efficacy of such a programme, results of QC tests and procedures relating to each element of the radiological imaging chain are presented and compared for four control visits carried out at 6 month intervals over a period of 2 years. A reduction of 50% (from 16 mGy to 7.5 mGy) of breast entrance doses (normalized to a breast thickness of 4.5 cm) and a significant improvement of detectability of high contrast details are discussed. The importance of encouraging an extension of a similar process to the other screening experiments currently underway in France is emphasized.

[Subareolar injection of 99m-Tc sulfur colloid for sentinel nodes identification in multifocal invasive breast cancer]. / Injection sous-aréolaire de sulfocolloïdes technétiés pour l'identification des ganglions sentinelles dans les cancers du sein invasifs à foyers multiples.

The objective were to study the relevance of the subareolar injection for sentinel node [SN] detection in multiple foci breast cancer. Seventy-nine patients with infiltrative breast carcinoma (diagnosed pre-operatively by core biopsy) and a mean age of 55 (31-78) years were enrolled. All patients were free of previous homolateral surgery, chemotherapy, locoregional radiotherapy or prevalent axillary lymph node. Using four 0.1 ml injections of 1.8 MBq, the technetium-99m 100 nm filtered sulfur colloid was injected by subareolar way (group I) in 16 cases of radiologically cancer with multiple invasive foci and 31 cases of radiologically unifocal cancer, and by peritumoral way (group II) in 32 cases of radiologically unifocal cancer. Scintigrams were obtained 2 to 4 hours after the injections and radioactive nodes were detected peroperatively 18 hours after the injection by intraoperative detection probe. Individual removal of all radioactive nodes was followed by axillary dissection at levels I and II of Berg including Rotter area control. All sentinel nodes were submitted to standard histopathological analysis on serial sections at 500 mu intervals completed by immunohistochemistry for cytokeratin on negative SN. SN were detected by scintigrams in 85% and 88% of the cases of group I and group II respectively, but in 98% and 97% of the cases of respectively both groups by intraoperative probe. Group I was composed of 69% ductal, 22% lobular and 9% tubular carcinomas, and group II of 87% ductal, 10% lobular and 3% tubular carcinomas. Seven and 5 radiologically unifocal tumors were in fact with multiple invasive foci at histology in groups I and II respectively. The complete scintigraphic procedure permitted the detection of a mean number of 2.7 (1-7) SN in group I and 2.3 (1-4) in group II (NS). In group I, the SN were metastatic in 22 patients (48%), 15 of them with the metastases being restricted to the SN, whereas in group II, the SN were metastatic in 9 patients (28%), 5 of them with the positivity restricted to the SN. No false negative result (SN negative and other axillary nodes positive) was observed in group I and only one false negative result in group II which was related to a cancer with histological multiple invasive foci. Sensitivities were 100% and 90%, and negative predictive values were 100% and 95%, for groups I and II respectively. Subareolar injection of radiocolloid allows identification of SN in cases of unifocal and multiple cancer. The mean number of SN detected by the subareolar method is not significantly different, although higher, to that detected by peritumoral injection.

[The role of cancer registries in the evaluation of breast cancer screening]. / Le rôle des registres de cancer dans l'évaluation des campagnes de dépistage du cancer du sein.

Cancer registries are necessary to evaluate the efficacy of cancer screening programmes. They provide early indicators of screening efficacy, needed to correct certain campaign failings without waiting for the mortality data, available only 7 to 10 years after the beginning of the screening. They allow to mesure the screening effect not only on the screened women, but also on the entire target population. They also allow to mesure the negative and deleterious effects of the screening. Finally, they are essential to all cost/efficacy study. The evaluation of the breast cancer screening programme in the French department of Bas-Rhin by the cancer Registry showed very quickly the interest of the mesures concerning the quality assurance programme and to estimate on the first screen results basis, that it will be difficult to reduce the mortality by breast cancer to 25%.

[Large sections in routine breast pathology. A technique adapted to conservative surgery]. / Les coupes larges en pathologie mammaire de routine. Une technique adaptée à la chirurgie conservatrice.

Large block macrosectioning of segmental excision specimens for breast cancer, and especially ductal carcinoma in situ, provides detailed information regarding size of the lesions, extent of spread and margin status which are essential for local recurrence risk assessment. However, the expansion of this technique has been curbed due to its reputation of being technically difficult, time-consuming, costly and providing slides of poor quality. We assessed the feasibility of the large section technique and adapted it to the everyday practice of a routine pathology laboratory. The time spent cutting a large block on a motorized microtome is half the time spent cutting the great number of conventional blocks needed to assess the same amount of tissue. Finally, 4 mm-thick stained large preparations of high quality are produced within 3 days after receiving the specimen. Analysis and report are both more precise and easier since the pathologist is saved the trouble of having to mentally re-assemble a great quantity of numbered small blocks. 805 primary monobloc segmental excision specimens have been examined in this way over the last 50 months period and we advocate its use as a standard procedure for breast-conserving surgery specimen management.

[Impact of menopause hormone replacement therapy on screening mammography reading]. / Impact du traitement hormonal substitutif de la ménopause sur la lecture des mammographies de dépistage.

PURPOSE: To assess difficulties in reading screening mammographies related to hormone replacement therapy (HRT) in the setting of a breast cancer screening program. Disagreement between two readers is used as the assessment criterion. POPULATION AND METHODS: The study population consisted of all women participating in the ADEMAS breast cancer screening program in Bas-Rhin (France). Agreement between the two radiologists was considered when the same global conclusion (call-back or not of the women for further examination) or the same conclusion for each of the nine possible lesions was observed. RESULTS: HRT is associated with a higher risk of disagreement between the two radiologists on global conclusion and on opacities. Conversely, disagreement risk is lowered for microcalcifications (whether benign or malignant) for HRT users. CONCLUSION: HRT is associated with a higher risk of disagreement on global conclusion. This has an impact on whether the women should be called-back or not according to reading of breast cancer screening program mammographies.

[The cost of breast cancer screening in France]. / Le coût du dépistage du cancer du sein en France.

PURPOSE: This paper presents the cost of two decentralised breast cancer screening programmes in France, in the Bas-Rhin and the Bouches du Rhône districts. Materials and methods. The costs directly related to running the two screening programmes were collected for the time period 1990-1997. Only direct costs of each programme, excluding assessment and treatment costs, are included in the cost analysis. Costs are presented per screening period, per programme attender and per cancer detected by screening. RESULTS: The screening programme costs an average of 397 francs per woman screened and 90,828 francs per cancer detected in the Bas-Rhin, and 379 francs and 76,159 francs, respectively, in the Bouches du Rhône. CONCLUSIONS: These costs are high compared to those of existing centralised programmes. Further research is needed to investigate means of ensuring the optimal efficiency of these programmes. The results of this study may help guide future decisions on the further development of breast cancer screening in France.

[A decentralized breast cancer screening program in the French department of Bas-Rhin]. / Un système décentralisé de dépistage du cancer du sein: l'exemple du Bas-Rhin en France.

Since 1989, in the French department of Bas-Rhin, a breast cancer screening program in going on and its results are presented here. This program, concerning women of 50 to 65 years-old, is decentralized, based on private or public radiologists and the motivation of women because there is no invitation. The interval between screening test is 2 years. After 8 years, the results are rather satisfactory: participation rate of the initial cohort is 77% in December 31st 1997, participation at incident screenings is above than 85%, early indicators (recall rate, detection rate, PPV of screening, PPV of biopsy) are improving with time to attain numbers like international studies. The ADEMAS program shows that a decentralized screening program, based on existing medical structures is possible in France. Anyway, it must be organized, evaluated at any time, with a quality assurance system to guarantee the women the best taking charge.

[Hormone therapy and chemotherapy of endometrial cancer]. / Hormonothérapie et chimiothérapie dans le cancer de l'endomètre.

It is correct to add hormone or chemotherapy in advanced metastatic disease of endometrial carcinoma and in recurrences. Large doses of hormone treatment have to be given. These are progestagens and the success rate with them, no matter which product is used, is approximately 30%. The use is limited by high blood pressure and the risks of vascular complications and metabolic upsets. Tamoxifen seems to the better tolerated and gives similar results. The response to hormone treatment depends on how sensitive the tumor is to the hormones. It is better when it has large numbers of progesterone receptors and it is of low grade. When the tumour is resistant to hormones, chemotherapy with cytotoxic drugs should be used. These drugs are adriamycine and mono or combined chemotherapy, but there is no protocol as yet that is better than any other. The debate about whether to use adjuvant treatment in stage I or II cases is open. It must be considered when the prognosis seems to be bad or there seem to be large risks of recurrences.

[The general practitioner and screening for cancer of the breast. Study of a sample of 200 general practitioners in the Bas-Rhin]. / Le médecin généraliste face au dépistage du cancer du sein. Enquête auprès d'un échantillon de 200 généralistes du Bas-Rhin.

A questionnaire survey of 200 doctors who were a sample of the general practitioners of the Bas-Rhin department was carried out. This was in order to ascertain what they knew about cancer of the breast and how they practised medically in this area, what were their doubts and what motivated them to screen for this kind of cancer? The questionnaire was found on the whole to acceptable. The enquiry showed that undoubtedly doctors were in favour of screening for cancer of the breast but were less enthusiastic carrying it out routinely. They also were unaware of ways in which such screening could be carried out (mammography being considered and examination which shows where the cancer was and not as a screening method). Furthermore, there was some confusion between screening and means of diagnosis. Results of this study show that it should be possible to outline the content and means of informing general practitioners about how to screen in order to enable them to participate in the Alsatian pilot campaign for screening for breast cancer.