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Resume But de l'etude L'amelioration spectaculaire de la survie des patients traites pour une maladie de Hodgkin (MH) a permis l'analyse du devenir des patients survivant a long terme. Ces derniers ont eu un certain nombre de complications, dont des neoplasies secondaires constituant le probleme le plus important. Plusieurs travaux recents font etat d'une augmentation de l'incidence des cancers du sein (CS) chez les jeunes femmes et les enfants traites pour une MH. Materiel et methodes Dans une etude retrospective realisee dans 11 centres de lutte contre le cancer, nous avons recense 63 femmes traitees pour MH et ayant ulterieurement developpe un cancer du sein. Nous avons analyse les resultats obtenus chez 13 patientes (21 %) qui ont eu un cancer du sein bilateral soit synchrone (cinq patientes), soit metachrone (huit patientes). L'âge moyen lors du traitement de la MH etait de 19 ans. Sept patientes avaient ete traitees par irradiation exclusive (comprenant une irradiation sus-diaphragmatiquedetype ≪ mantelet ≫ et six par association chimiotherapie-radiotherapie. Resultats Le delai moyen d'apparition du premier cancer du sein a ete de 16 ans. Selon la classification TNM, on notait: neuf tumeurs de stade T0, quatre tumeurs de stade T1, cinq tumeurs de stade T2, une tumeur de stade T3, deux tumeurs de stade T4 et cinq tumeurs de stade Tx; il y avait 17 carcinomes infiltrants, deux fibrosarcomes et sept carcinomes canalaires in situ. Un envahissement ganglionnaire a ete retrouve dans dix des 15 curages realises pour des cancers infiltrants. Globalement, 17 tumeurs ont ete traitees par chirurgie radicale et neuf par association radiochirurgicale conservatrice. Avec un suivi moyen de 70 mois (extremes: 15–125), trois patientes ont eu une recidive locale et/ou regionale et quatre des metastases. Huit patientes etaient en vie sans signe de maladie et une est decedee d'affection intercurrente. Conclusion Dans la litterature, les cancers du sein representent de 6,3 a 9 % des neoplasies secondaires apres traitement pour MH, mais le risque est beaucoup plus eleve chez les jeunes filles traitees avant 20 ans, et plus particulierement avant 15 ans. Les facteurs favorisants sont: l'irradiation, la jeunesse lors du traitement, la chimiotherapie par agents alkylants, et peut-etre des facteurs genetiques. Ces femmes doivent beneficier d'une surveillance senologique tres reguliere et prolongee, cela au minimum des la fin de la 10e annee apres la fin du traitement de la MH. Un traitement conservateur pour ces cancers du sein secondaires est parfois possible.

In a retrospective multicentric analysis, 63 women treated between 1941 to 1988 for Hodgkin's disease (HD) subsequently developed 76 breast cancers (BC). The median age at diagnosis of HD was 26 years (range 7-67), and 22 women (35%) were 20 years old or less. Exclusive radiotherapy (RT) was used in 36 women (57%) and combined modalities with chemotherapy (CT) in 25 (39%). Breast cancer occurred after a median interval of 16 years (range 2-40) and the median age at diagnosis of the first BC was 42 years (range 25-73). TNM classification (UICC, 1978) showed 10 T0 (non-palpable lesions) (13%), 20 T1 (26%), 22 T2 (29%), 8 T3 (11%), 7 T4 (9%) and 9 Tx (12%), giving altogether a total of 76 tumours, including, respectively, 5 and 8 bilateral synchronous and metachronous lesions. Among the 68 tumours initially discovered, 53 ductal infiltrating, one lobular infiltrating and two medullary carcinomas were found. Moreover, two fibrosarcomas and 10 ductal carcinoma in situ (DCIS) were also found. Among 50 axillary dissections for invasive carcinomas, histological involvement was found in 31 cases (62%). 45 tumours were treated by mastectomy, without (n = 35) or with (n = 10) RT. 27 tumours had lumpectomy, without (n = 7) or with RT (n = 20). 2 others received RT only, and one only CT. 7 patients (11%) developed isolated local recurrence. 20 patients (32%) developed metastases and all died; 38 are in complete remission, whereas 5 died of intercurrent disease. The 5-year disease-specific survival rate by the Kaplan-Meier method was 61%. The 5-year disease-specific survival rate for pN0, pN1-3 and pNor = 3 groups were 91%, 66% and 0%, respectively (P0.0001) and 100%, 88%, 64% and 23% for the T0, T1, T2 and T3T4 groups, respectively. These secondary BCs seem to be of two types: a large number of aggressive tumours with a very unfavourable prognosis (especially in the case of pN3 and/or T3T4); and many tumours with a 'slow development' such as DCIS and microinvasive lesions, especially in patients treated exclusively by RT. Moreover, a very unusual rate of bilateral tumours (21%) was observed. These secondary BC could be 'in field', in 'border of field' or 'out of field'. However, a complete analysis of doses delivered by supradiaphragmatic irradiation was often very difficult, due to large variations in several parameters. We conclude that young women and girls treated for HD should be carefully monitored by clinical examination, mammography and ultrasonography.

Though Hodgkin's disease (HD) is one of the malignancies in which considerable progress has been made, long-term side effects have been observed, second primary cancer being the most significant. Several recent reports have indicated an increased risk of breast cancer (BC) in girls and young women among HD patients.In a retrospective multicenter analysis, 63 women treated for HD subsequently developed BC. Results that were obtained in 13 women (21%) who developed either synchronous (five cases) or metachronous (eight cases) BC were analyzed. The median age at diagnosis of HD was 19 years. Seven patients underwent exclusive radiotherapy (RT) (including "mantle" supradiaphragmatic irradiation) and six received concomittant radiation therapy and chemotherapy.The first breast tumor occurred after a median delay of 16 years. According to the TNM classification, we showed nine stage T0 (non palpable lesions), four stage T1, five stage T2, one stage T3, two stage T4 and five stage Tx BC. Seventeen infiltrating carcinomas, two fibrosarcomas and seven ductal carcinomas in situ were observed. Among 15 axillary dissections performed for invasive carcinomas, histological involvement was found in 10 cases. Seventeen tumors were treated by mastectomy and nine patients underwent conservative surgical treatment. With a 70-month median follow-up (range: 15-125), three patients developed locoregional recurrence and four other metastases. At present, eight are alive with no evidence of disease and one died of intercurrent disease.According to previous works, BC represents 6.3 to 9% of all second cancers occurring after HD treatment. The risk is higher in young women treated before 20 years of age, especially before 15 years of age. Factors that favour the development of secondary BC are: supradiaphragmatic irradiation, very young age at treatment, chemotherapy with alkylating agents, and probably genetic factors. We conclude that young women and girls treated for HD should be carefully monitored at least 10 years after the end of the treatment for HD, using clinical examination, mammography and ultrasonography. The optimal rythm of this follow-up is not yet clearly defined. Moreover, after multidisciplinary concertation, we suggest that secondary BC be sometimes treated by conservative radiosurgical approach.

From 1960 to 1986, 397 cases of non-metastatic male breast cancer (MBC) treated in 14 French regional cancer centres were reviewed. The median age was 64 years (range 25-93). TNM classification (UICC, 1978) showed seven T0, 79 T1, 162 T2, 31 T3, 74 T4 and 44 unclassified tumours (Tx). Clinical positive lymph nodes were found in 31% of the patients. 24 patients received radiotherapy only, and 373 underwent surgery, 247 of these with postoperative irradiation. Adjuvant chemotherapy and hormonal therapy were used in 71 and 68 patients, respectively. There were 382 infiltrating carcinomas and 15 pure ductal carcinoma in situ. Lymph node involvement was found in 56% of infiltrating carcinoma. The oestrogen (ER) and progesterone (PgR) receptors were positive in 79% and 77%, respectively, of examined cases. Isolated local and regional recurrence were observed in 8.8% and 4.5% of cases, respectively and 40% of patients developed metastases. The crude survival rates by Kaplan-Meier method were 65% and 38% at 5 and 10 years, respectively, and the disease-specific survival rates (without death due to intercurrent disease or second cancer) was 74% at 5 years and 51% at 10 years. The disease-specific survival rate for pN- and pN+ groups were 77% and 39% at 10 years. The prognostic factors were clinical size (T) and histological axillary status (pN-/pN+). The relative risk of death for pN- was 1.0, 2.0 and 3.2 in the T0-T1, T2 and T3-T4 groups, respectively. For pN+, these relative risks increased 1.9, 3.9 and 6.0 in the same groups. The optimal treatment include modified radical mastectomy and irradiation for cases with risk factors of local relapse (nodal invasion, large tumour with cutaneous or muscular involvement). Locoregional failure had unfavourable prognosis. First-line adjuvant treatment seems to be tamoxifen, due to the very high rate of positive hormonal receptors and the old age of the patients, which contraindicate chemotherapy in many cases. The prognosis of patients with breast cancer is the same in male and female patients when disease-specific survival rate, tumour size and axillary involvement are compared.

This retrospective study shows the advantage of the CA 15.3 assay for the early detection of relapse in breast cancer. It involved 473 women with invasive canalar carcinoma who had local recurrence or metastasis and/or an elevation of CA 15.3 (35 kU/l). The positive predictive value is excellent (97.7%). Sensitivity is poor for local relapse (13.7%), but a marker elevation at this time is a good prognostic factor of further distant metastasis (88%). It is better in the case of distant metastasis (74%), especially in bone and and liver localizations. CA 15.3 measurement at two month intervals may allow an early detection in 40% of distant metastasis. These results confirm the need of trials to test the benefits in terms of survival of early treatment of breast cancer metastasis only proved by CA 15.3 elevation, without any clinical or radiological finding.

Male breast cancer represents about only 1% of all breast cancers. We have analysed a retrospective, multicentric series of 404 patients, initially non-metastatic, with mean age of 63 years. The 5 and 10-year overall survival rates were 65 and 36% respectively. Sixty-eight patients developed secondary cancer. From ten patients who already presented with cancer (2.5%) 3 cases corresponded to prostatic cancer treated by estrogen. Four had synchronous cancer (1%). Three and eight patients respectively had a synchronous and metachronous contralateral breast cancer (2.7% of bilateral cancer). Forty-three other patients (10.6%) developed metachronous cancer. The main tumor types were: prostate (9), lung (6), colon and rectum (6), esophagus (4). Four patients developed various hematologic malignancies and 14 patients, various types of solid tumors. From these 43 patients, 27 died; 19 as a result of secondary cancer. This represents 9% of all deaths among the 404 patients. While the bilateral cancer rate is similar to women, the second cancer rate appears to be higher in men. From hematological malignancies, chemotherapy and radiotherapy do not seem to contribute to this high incidence of second cancer.

Ductal carcinoma in situ of the breast is very rare in men, representing 0-7% of all male breast cancers. We analysed 15 cases from a retrospective multicentric series of 404 patients (3.7%). It occurs earlier than infiltrating carcinoma (mean age: 55 years), sometimes before 40 years of age. The main symptoms are bloody nipple discharge or retro areolar mass. Modified radical mastectomy constitutes the basic treatment. Lower axillary dissection can eventually be indicated in comedocarcinoma or in tumors larger than 25 mm. The main histologic subgroup is papillary carcinoma, pure or intracystic. As is the case in women, local recurrence, invasive or not, rarely occurs. Theoretically, the cure rate approaches 100%. However, as in all cases of breast cancer in men, an important number of deaths due to secondary cancer or intercurrent disease have been noted. Until now, no clear etiologic factors have been found.

Material From 1960 to 1990, 581 cases of male breast cancer (MBC) were reviewed in 19 Cancer Institutes in France. 23 (4%) were pure DCIS. The median age was 56.5 years (ext. 26–77). Five patients had less than 40 years (22%). Gynecomastia was found in 10 out of 23 patients (43%). Three had family history of B. C. According to TNM classification, we found 6 impalpable lesions (T0) discovered by serosanguineous nipple discharge, 7 T1, 6 T2, and 4 Tx. Treatment The surgery consisted of 3 lumpectomies, 16 modified, 2 subcutaneous and 2 radical mastectomies. 16 patients had axillary dissections and 6 irradiation on the chest wall. Histology All cases were pure DCIS: in 14 the subtype was clearly identified: papillary (4), papillary intracystic (3), mixed papillary and cribriform (3), comedocarcinoma (2), cribriform (1), apocrine (1). Three patients had local recurrences: two occurred in the patients initially treated by lumpectomy alone: the first was again a DCIS, but the second was an infiltrating carcinoma; this patient died by metastases. The last relapse occurred on the chest wall in a patient treated by mastectomy. One patient developed a contralateral DCIS. Two patients developed a lung and kidney cancer respectively. In the literature the rate of DCIS in man varies from 0 to 16%. The serosanguineous nipple discharge seems a frequent symptom, especially in young men. The main histologic subtype is papillary (pure or intracystic). Mastectomy is the treatment of choice.

Introduction The second cancers represents the most important problem among the survivors of HD. A possible link with chemotherapy (CT) and radiotherapy (RT) is suggested but genetic and immunologic factors may also be involved. Material In seven Cancer Centers, we found 35 women, previously treated for HD, who developed 37 BC. The median age at diagnosis of HD was 25 years, with 12 less than 20 years. HD stage was: 1 = 3, II = 21, III = 5, IV = 4, NS = 2. 33 women received supradiaphragmatic RT with doses varying from 35 to 45 Gy. 16 women received CT (mainly MOPP). The median interval between the diagnosis of HD and BC was 16 years. According to TNM, we found: 2 T0, 10 Tl, 12 T2, 4 T3, 6 T4 and 3 Tx. 32 were ductal infiltrating carcinoma, 2 medullary, 2 in situ and one fibrosarcoma. Axillary involvement was present in 51% of cases. Mastectomy was performed in 23 cases, a radiosurgical conservative treatment in 12 and exclusive radiotherapy in 2. Fourteen women underwent chemotherapy. Results 7 women had local relapse of BC and 15 had metastases (40%). Three had contralateral metachronous BC. 17 women are in complete remission for both diseases; 15 died of BC. Three women died of intercurrent disease. Conclusion The women treated for HD, especially before 20 years, seem to have an increased risk of subsequent BC. According to other reports, we confirm that these BC are frequently aggressive, with rapid evolution and high risk of bilaterality. Consequently, a regular mammographic follow-up is necessary to detect these lesions earlier, to allow a better prognosis and a possible conservative treatment.

Between May 1978 and March 1982, 179 postmenopausal women with operable breast cancer were randomized to receive either adjuvant tamoxifen, 40 mg daily for three years (TAM group), or no further treatment (controls). The difference in five-year survival rates (61% in the control group, 72% in the TAM group) was not statistically significant. However, there was a significant improvement in disease-free survival in the TAM group (61%) relative to the controls (44%) (p = 0.008). In estrogen receptor positive patients, tamoxifen improved both the disease-free rate (47% controls, 80% with tamoxifen) and the survival rate (63% to 83%). Similar results were observed in progesterone receptor positive patients. In patients that were estrogen receptor negative, tamoxifen modified neither the survival rate nor the disease-free interval.

This study concerns 645 patients first treated with surgery for unilateral, non metastatic, invading breast cancer. Intratumoral estrogen receptor and progesterone level were determined in every case. Level greater than 5 fmoles/mg cytosolic protein was considered as positive for both receptors. Univariate analysis has pointed out a significant linkage between overall survival and the following factors: age, clinical size of the tumor, histopathological grading SBR, clinical and histological lymph node involvement, capsular tear, RO and RP status. Statistical significance of menopausal status is borderline. Number of tumor foci is not significant. Likewise, disease free survival was correlated to the same factors. Multivariate analysis (Cox), secondarily pointed out that overall survival was strongly related to age, size of the tumor, lymph node involvement, capsular tear, histopathological grading SBR, menopausal status and RP. Multivariate analysis of the disease free survival revealed that it was strongly related to age, tumor size, lymph node involvement, capsular tear, grading SBR and RP. An interaction has been pointed out between Ro and menopausal status: Ro greater than 5 fmoles/mg cytosolic protein carry its own prognostic weight (Cox) and lengthen overall survival only for post menopausal women. A prognostic score, taking into account all of these factors has been calculated for both overall survival and disease free survival, and enabled us to isolate 4 groups of patients with good, intermediate and bad prognosis. These 2 models have been validated on an independent group of patients according to the sample test procedure. This results indicate that hormonal receptors carry their own prognostic weight in operable breast cancer (only for postmenopausal women for RO), and should be taken into account when adjuvant therapies are indicated after surgical treatment for breast cancer, in association with other more usual prognostic factors.

The so-called inflammatory carcinoma of the breast is a rare condition characterized, in almost every case, by metastatic diffusion in numerous organs. Clinical criteria are indispensable to establish a diagnosis which is not ruled out by a negative skin biopsy. Radiotherapy or surgery, or both, gives disappointing results with a median survival of about 18 months and a 5-year survival rate of 5%. It is unanimously agreed that adding chemotherapy to these methods improves local control and increases the 5-year survival rate. The optimal treatment remains to be determined by co-operative studies.

The diagnostic value of mammography was evaluated retrospectively in 23 recurrent carcinomas in patients previously treated by partial mastectomy with or without adjuvant radiotherapy. Mammography established accurate diagnosis in 11 of the 23 patients. Mammography should always be performed in addition to clinical and cytological examinations and results must be evaluated jointly. Confrontation of these three investigations may be inconclusive as a result of changes produced by radiotherapy or surgery. The authors recall the necessity of surgical control of any nodular lesion developed in the area of the initial operation, particularly during the first three years.

Between October 1977 and December 1983, 379 consecutive patients have been treated for unilateral, non metastatic breast cancer, either with conservative (n = 205) or radical surgery (n = 174), with axillary dissection in all the cases. None of them had histologically proved lymph node involvement. Adjuvant radiotherapy was given in 268 cases. Estrogen receptor (ER) and progesterone receptor (PR) levels were measured on each tumor. Levels greater than 5 fmoles/mg cytosolic protein were considered as positive for both ER and PR. At 5 years, overall survival (OS) and disease-free survival (DFS) are respectively 88% and 79%. Unifactorial analysis using KAPLAN and MEIER estimates and Logrank test revealed that OS was significantly related to age, tumor size, histopathological grading, ER and PR. DFS was significantly related to the same factors. Menopausal status, number of intra mammary tumor foci, previous familial history of breast cancer were not significant. Multifactorial analysis revealed that DFS was significantly related to age (bad prognosis [bp]: less than or equal to 37 years old), tumor size, histopathological grading (bp: SBR = 3) and that OS was significantly related to tumor size and PR (bp: PR less than or equal to 5 fmoles/mg protein). A prognostic score was obtained which sampled our patients into 3 significantly different (P less than 0.0001) groups with high, intermediate and low risk of relapse. These results suggest that tumor size, histopathological grading and PR have their own prognostic weight in histologically node negative breast cancer. Grouping these factors together allows to define a high risk relapse group that could benefit from adjuvant treatment.