Guidelines on the standards for the training of specialised health professionals dealing with breast cancer.

According to EUSOMA position paper 'The requirements of a specialist breast unit', each breast unit should have a core team made up of health professionals who have undergone specialist training in breast cancer. In this paper, on behalf of EUSOMA, authors have identified the standards of training in breast cancer, to harmonise and foster breast care training in Europe. The aim of this paper is to contribute to the increase in the level of care in a breast unit, as the input of qualified health professionals increases the quality of breast cancer patient care.

European guidelines for quality assurance in the surgical management of mammographically detected lesions. European Breast Cancer Working Group.

The European Guidelines developed for mammography screening have contributed to the general discussion on quality assurance and the important tasks of the health professionals dealing with breast cancer screening. The cooperation of each medical discipline is of utmost importance in order to achieve optimal results and eventually a mortality reduction. The following guidelines are based on the British NHS quality assurance guidelines for surgeons in breast cancer screening and modified to meet the different needs in the European Countries. The term "surgeon" denotes a medical doctor trained and involved in the surgical treatment of breast diseases. The members of the working group who participated in order to adapt these guidelines are listed above. We hope that this document will contribute towards a more comprehensive approach of breast cancer screening-detected lesions throughout Europe.

[Breast-preserving treatment of breast cancer and peroperative curietherapy]. / Traitement conservateur du cancer du sein et curiethérapie peropératoire.

From May 1988 to December 1990, 35 patients benefitted from a breast-conserving treatment (tumor resection with at least 1 cm of free margin, axillary dissection and peroperative brachytherapy). The iridium sources were introduced 24 h later, delivering between 15 to 17.5 Gy. Three weeks later an additional course of external radiation delivered a dose of 50 Gy in 5 weeks to the whole breast. In this series, only very early breast lesions were included and no patient received additional chemotherapy. Due to the short period of observation, we only report on the acute side effects even if until now we have not seen any case of tumor relapse. We did not observe any major complications after this combined approach: only three patients developed a local infection requiring antibiotics. Esthetic evaluation is quite encouraging with all women showing good and excellent results from the physician's and patient's points of view. This approach seems to be quite interesting cosmetically as it allows to correct the breast shape while preserving an adequate position of the implant and so preserving a good oncological approach.

[Morbidity of surgical treatment for advanced cancer of the breast after irradiation]. / Morbidité du traitement chirurgical du cancer due sein avancé après irradiation.

The authors reviewed the medical files of 100 patients with locally advanced breast cancer (stage III), treated in the department of surgery of the Institut Jules-Bordet between 1974 and 1988. All patients received preoperative radiotherapy (average total dose of 45 Grays). This preoperative irradiation was associated with chemotherapy in 74% of patients. All patients subsequently underwent surgery and a modified radical mastectomy was performed in 92% of cases. Our data analysis reveals an incidence of 25% of local wound infections, 34% of delayed wound healing, 63% of seroma formation and 22% of lymphoedema of the upper limb. The local postoperative morbidity appears to be increased in patients preoperatively irradiated. This indicates that preoperative chemotherapy may be preferable in these patients to minimise the local postoperative morbidity and its impact on the quality of life.

Local postoperative morbidity following pre-operative irradiation in locally advanced breast cancer.

The authors have reviewed the medical files of 100 patients with locally advanced breast cancer (Stage III), who were treated in the Department of Surgery at the Institut Jules Bordet between 1974 and 1988. All patients received pre-operative radiotherapy (average total dose 45 Gy), which was associated with chemotherapy in 74% of patients. All patients were subsequently subjected to surgery, using a modified mastectomy in 92% of cases. Our data reveal an incidence of 25% local wound infection, 34% delayed wound healing, 63% seroma formation and 22% lymphoedema of the upper limb. It seems that local postoperative morbidity is increased in patients pre-operatively irradiated. This indicates that pre-operative chemotherapy may be preferable in these patients to minimize the local postoperative morbidity and its impact on the quality of life.

Axillary dissection in breast cancer revisited.

The pathological status of the axillary nodes remains the single most determining factor for survival, local recurrence and disease-free interval in operable breast cancer. Radical axillary dissection results in better local control with or without systemic disease in all operable cases. In pathologically negative cases, radical axillary dissection decreases local recurrence rates and perhaps prolongs disease-free survival. In pathologically positive cases, radical axillary dissection improves local control only. Radical axillary dissection avoids axillary irradiation and so decreases the risk and the importance of lymphoedema. Perfect axillary dissection does not show a decisive advantage over less complete axillary dissection when the 'quality' of surgery is measured by lymphoscintigraphy, but it should be kept in mind that only total control of the local situation can ensure a patient free of distal spread at the time of first therapy.

Relationship between computerized morphonuclear image analysis and histopathologic grading of breast cancer.

A pilot study analyzed the relationship between several morphonuclear parameters and the Bloom-Richardson score for 37 invasive, not-otherwise-specified (NOS) ductal breast carcinomas. The SAM-BA 200 cell image processor and its software were used to measure the nuclear features on Feulgen-stained imprint smears. Two parameters representing the numbers of large and dense chromatin clots and two parameters describing the heterogeneity of the chromatin among nuclei in a specimen evolved in a continuous manner parallel with the Bloom-Richardson score from stages NOS-4 to NOS-8. The systematic measurement of these four parameters on a large series of breast cancers may be able to define an objective and reproducible "scale" of differentiation that could be a helpful tool for pathologists and clinicians.

Locoregional recurrences after 649 modified radical mastectomies: incidence and significance.

A continuous series of 649 patients, treated by modified radical mastectomy for primary breast carcinoma, is analyzed after a median follow-up of 92 months. 'True isolated' locoregional recurrences (LR), defined as LR not preceded or followed by distant metastases within 6 weeks, appeared with a cumulative actuarial incidence rate of 6%, 14% and 19% after 1, 5 and 7 years respectively, whereas the respective figures for distant metastases (M1) were 10%, 37% and 48%. The main initial parameters, predicting both the LR-free and the M1-free interval, are presented by statistical analyses in the following order of importance: number of invaded lymph nodes in the axilla, tumor size (T) and histological grading of differentiation. The same factors also predicted the imminence of M1 once LR had occurred, as well as survival after LR. A higher incidence of M1 after LR was also correlated with estrogen-receptor negative tumors and with those LR occurring within one year after mastectomy. LR occurred at the chest wall (65%), in the sub-clavicular fossa (16%) and the axilla (6%); the remaining 13% occurred in two of the sites. There was a trend towards longer survival after chest wall recurrence than after LR recurrence at another site. Axillothoracic irradiations postmastectomy gave a lower rate of LR in 227 patients than did a regimen of 12 months adjuvant chemotherapy with irradiation restricted to the internal mammary lymph nodes in 120 subsequent patients: 17 vs 25% at 5 years (P = 0.03 when adjusted by initial nodal involvement and T-size). Total excision of LR (repeated if new LR occurred) gave better rates of local ultimate control and survival than other kinds of treatments, with or without adjuvant local or systemic therapy. LR is not always a sign of imminent generalized disease. Actuarial 5-year survival after LR is 26.2% overall whereas, if only 'true isolated' LR are considered, the survival is 37%.

Correlation between nuclear cytomorphometric parameters and estrogen receptor levels in breast cancer.

The authors studied the relationships existing between various cytomorphonuclear parameters recorded on 25 primary breast cancers and their estrogen receptor (ER) content. Cell image analyses of Feulgen-stained imprint smears, allowing determination of morphologic, densitometric, as well as textural parameters, were assessed by using the SAMBA 200 system (TITN, France). The ER levels were measured by the conventional dextran-coated charcoal assay. The authors then divided the 25 cancers into three categories: (1) "ER-negative or poorly positive tumors," i.e., those having less than 50 fmol ER/mg protein; (2) "ER-positive tumors," i.e., those containing between 50 and 150 fmol ER/mg protein; and (3) "ER highly positive tumors," i.e., those having more than 150 fmol ER/mg protein. The authors' results show that ER-negative or poorly positive breast cancers possess cells with bigger nuclei and higher DNA content, related to higher proliferation index than ER-rich tumors. Furthermore, the chromatin pattern of cells from ER-negative or poorly positive breast cancers is significantly more condensed than the thinly textured chromatin of ER highly positive tumors. Cell image analysis of Feulgen-stained imprints is proposed as an additional tool for grading malignancy.

In vitro influence of estradiol or progesterone on the thymidine labeling indices of human benign breast tumors.

Using an in vitro tritiated thymidine (3H-dThd) nuclear labeling followed by autoradiography, the effects of 17-beta-estradiol (E2) or progesterone (Pg) on cell proliferation were studied in 22 human benign breast tumors, i.e. 7 fibroadenomas 8 fibrocystic dysplasias 4 gynecomastias and 3 phyllodas. Small tumor fragments were incubated in a chemically-defined medium without serum and were hormonally stimulated in vitro. The procedure used allowed discrimination between weak labeling, suggestive of DNA repair mechanism, and strong labelling, suggesting a true DNA synthesis (S phase). Taking this into account, our results have shown that both estradiol and progesterone can induce in vitro cell replication of both ER+PgR+ and ER-PgR- human breast fibroadenoma, without affecting those of fibrocystic dysplasia, gynecomastia and phylloda. Progesterone, but not estradiol, might significantly decrease DNA repair mechanism in fibrocystic dysplasia, according to the Pg-induced decrease of nuclear incorporation of small amounts of 3H-dThd. We have thus characterized a dynamic test of hormone dependence which permits in vitro study of the hormonal sensitivity of human benign breast tumors, as well as that of any other human neoplasm. This test could be of great value to help clinicians to diagnose and treat hormone-dependent neoplasms properly. Its clinical relevance is now under study.

Relation between estrogen receptor concentration and clinical and histological factors: their relative prognostic importance after radical mastectomy for primary breast cancer.

After modified radical mastectomy, 490 primary breast cancer patients were followed for a median of 75 months. Bloom grade was measured in 340 patients and ER status in 341. Follow-up of these patients has yielded the following results: (a) The value of traditional indices has been reaffirmed. (Cox's multivariate analysis identified, in order of decreasing importance, the number of invaded lymph nodes, the initial tumor size and the histological grade. Other variables were found to be of lesser importance and were correlated with the three main indices.) (b) The value of ER status disappeared after more than 3 years of follow-up. (c) ER positive patients fared better after recurrence. This was interpreted as being a consequence of their responsiveness to hormonal treatment.

Six-year results of a multimodality treatment strategy for locally advanced breast cancer.

Between 1976 and 1982, 59 patients with locally advanced breast cancer were treated with preoperative supervoltage radiotherapy, adjuvant preoperative and postoperative hormonochemotherapy, and modified radical mastectomy. Systemic treatment, which was started simultaneously with radiotherapy, consisted of a combination of daily oral tamoxifen and a monthly alternation of Doxorubicin + vincristine and cyclophosphamide + methotrexate + 5-fluorouracil (CMF). One of each cycle was given preoperatively at half dosage and five of each were repeated postoperatively at full dosage. All patients became operable. Results of pathologic examination of the operative specimen, available in 51 patients, showed complete disappearance of tumor tissue in breast areas in eight patients, of which three still had positive axillary nodes. After a median follow-up time of 6 years locoregional failure was observed in 12 patients (20%) but in only three (5%) did it occur before distant failure. The actuarial median survival of the entire patient population is close to 4 years. Seven patients are alive without recurrence at greater than 9 years. This aggressive multidisciplinary treatment approach is associated with a projected 30% long-term survival (10 years), excellent local control, but substantial toxicity.

[Development of a therapeutic strategy and role of surgery in breast cancer]. / Evolution de la stratégie thérapeutique et rôle de la chirurgie dans le cancer du sein.

The evolution of therapeutic strategy and the role of surgery in breast cancer. Loco-regional control of breast cancer is achieved with lesser surgical mutilation. Quality of results is however dependent of the stage of the disease more than of therapeutic modalities.