The importance of using computed tomographic scanning in breast irradiation after conservative treatment

Fanconi anaemia (FA) is an autosomal recessive disease characterized by bone marrow failure, variable congenital malformations and predisposition to malignancies. Cells derived from FA patients show elevated levels of chromosomal breakage and an increased sensitivity to bifunctional alkylating agents such as mitomycin C (MMC) and diepoxybutane (DEB). Five complementation groups have been identified by somatic cell methods, and we have cloned the gene defective in group C (FAC)(7). To understand the in vivo role of this gene, we have disrupted murine Fac and generated mice homozygous for the targeted allele. The -/- mice did not exhibit developmental abnormalities nor haematologic defects up to 9 months of age. However, their spleen cells had dramatically increased numbers of chromosomal aberrations in response to MMC and DEB. Homozygous male and female mice also had compromised gametogenesis, leading to markedly impaired fertility, a characteristic of FA patients. Thus, inactivation of Fac replicates some of the features of the human disease.     

Unresolved questions in the indications for the conservative treatment of invasive cancer of the breast

The majority of patients with breast cancer can be treated by partial mastectomy and radiation therapy. The choice of the treatment involves the estimation of the risk for intramammary recurrence and the ability to achieve satisfactory cosmetic result. Patient selection in breast conserving therapy is dependent on clinical and histologic characteristics of the tumor, but many times the therapeutic decision is not easy. We present a review of the literature in order to try to resolve some controversed questions about breast conservation in relation to tumor size, margin status, tumor location, multicentricity, histologic subtype or presence of extensive intraductal component, age of patients and genetic factors.     

Influence of locoregional irradiation on local control and survival in breast cancer

A profiling ELISA was developed to detect antibody to the non-structural (NS) proteins Lb, 2C, 3A, 3D, and the polyprotein 3ABC, of foot-and-mouth disease virus (FMDV). The assay was used to examine panels of sera from naive cattle, and from experimentally infected or vaccinated animals. All sera from cattle experimentally infected with any of the seven serotypes of FMDV were positive for antibody to 2C, 3A, 3D and 3ABC, and the majority were positive for Lb. The three categories of sera could be differentiated on the basis of the presence or absence of antibody to the structural and/or NS proteins of FMDV. The assay is simple, rapid and reproducible and can be used to identify previous infection in animals which are seropositive for antibody to the structural proteins of the virus. Validating the assay with field sera demonstrated that antibody to 3ABC, and usually one or more of the other non-structural proteins, was detected only in animals reported to have shown clinical signs of FMD. Vaccinated cattle which had received less than five vaccinations, were frequently positive for antibody to 3D but were negative for antibody to 3ABC. Occasional animals which had received more than ten vaccinations had NS protein antibody profiles which were similar to those seen following infection.     

The effects of postradiation treatment with tamoxifen on local control and cosmetic outcome in the conservatively treated breast

BACKGROUND: The aim of this study was to evaluate the impact on disease recurrence and cosmetic outcome of tamoxifen treatment initiated after breast-conserving therapy (BCT). METHODS: Between 1982 and 1994, 498 women (509 breasts) were treated with BCT in accordance with a highly standardized institutional protocol. Adjuvant tamoxifen was administered to 130 patients (134 breasts), beginning 1-6 weeks after irradiation. The median ages and duration of follow-up for groups who received tamoxifen (TAM+) and no tamoxifen (TAM-) were 62.5 years/56 months and 53 years/60 months, respectively. The members of the TAM+ group were significantly older (P = 0.0001) and had increased incidences of positive axillary lymph nodes or undissected axilla (P = 0.001). There was a significant (P = 0.001) difference between the TAM+ and TAM- groups in the distribution of histopathologic subtypes; this reflected an increased proportion of associated ductal carcinoma in situ in the TAM- group. More extensive regional lymphatic irradiation was administered to the TAM+ group. Chemotherapy was administered to 15% of TAM+ and 28% (P = 0.003) of TAM- patients. There were no significant differences between the groups with respect to tumor size, reexcision, total excised tissue volume, final margin status, total radiation dose, or use of interstitial implant boost. RESULTS: There was no significant difference between the TAM+ and TAM- groups in the overall distribution of cosmetic scores (P = 0.18). The 5-, 7-, and 10-year actuarial local failure rates for TAM+ versus TAM- patients were 0% versus 3.1%, 1.9% versus 5.4%, and 1.9% versus 8.4%, respectively. Multivariate regression analyses of potentially confounding variables revealed no significant associations between tamoxifen and either cosmetic outcome or local failure. CONCLUSIONS: Radiotherapy followed by tamoxifen has no adverse interactive effect on cosmesis, and tamoxifen is associated with a trend toward enhanced 5-year local control probability.     

Adjuvant radiation after conservative surgery for early breast cancer. Local control and cosmetic outcome

Between 1980 and 1987, 115 patients with early breast cancer underwent conservative surgery and radiation therapy. Median follow-up from the date of surgery was 48 months. There was local recurrence in 5 of the 115 patients. Of this group, 67 patients were evaluable for cosmetic outcome. The overall cosmetic result was judged by a panel to be excellent or good in 61%, fair in 27%, and poor in 12%. Patients themselves found the cosmetic result to be excellent or good in 94%. Retraction of the inferior border of the breast, surface difference between both breasts, breast induration, scar retraction and telangiectasia correlated with the cosmetic score. Type of surgery, axillary irradiation, use of bolus, and length of follow-up all influenced the cosmetic outcome in a univariate analysis.     

The impact of treatment time and smoking on local control and complications in T1 glottic cancer

Low frequency impedance measurements of pure egg lecithin (phosphatidylcholine) bilayers have revealed the presence of four layers which can be attributed to the acyl chain, carbonyl, glycerol bridge and phosphatidylcholine regions of the lecithin molecule. Measurements on bilayers formed in the presence of unoxidised-cholesterol revealed that cholesterol molecules were located in the hydrocarbon region of the bilayer with its hydroxyl groups aligned with the carbonyl region of the lecithin molecules. Measurements of oxidised-cholesterol lecithin bilayers revealed that these molecules protruded less into the hydrocarbon region and their polar hydroxyl group aligned with the glycerol bridge region of the lecithin molecule.     

Lobular carcinoma in situ of the breast: results of a radiosurgical conservative treatment

From 1980 to 1992, 17 women underwent lumpectomy (13) or quadrantectomy (4) and whole breast irradiation (median dose: 52 Gy) for pure lobular carcinoma in situ (LCIS). Three cases correspond to palpable lesions and 14 were discovered only by mammography. Twelve women also received tamoxifen at 20 mg/day for two years. With a median follow-up of 88 months, no local or regional recurrences have been recorded. The global rate of bilateral carcinoma was 17.6% (2 synchronous and one metachronous). In the literature, only eight other cases of LCIS were treated by lumpectomy and radiation therapy, but without details and data on long-term results. After biopsy alone for LCIS subsequent infiltrating carcinoma occurred in about 15% of the cases. Thus, the classical radiosurgical association should represent an interesting alternative both for biopsy alone and radical surgery until now only proposed to treat LCIS.     

The importance of steroid receptors for the prognosis and hormone treatment of breast cancer patients: a retrospective study in Southeastern Netherlands

OBJECTIVE: To assess the effect of oestrogen (ER) and progesterone (PgR) receptors on the prognosis of patients with operable breast cancer and the decision to treat these patients with adjuvant tamoxifen. DESIGN: Retrospective. SETTING: Eight community hospitals in the Southeast Netherlands. METHOD: Using the registry of the Comprehensive Cancer Centre South, 2862 breast cancer patients were identified with stage I, II or IIIA tumours, treated during the period 1984-1992. RESULTS: ER and PgR status were known for 2393 (84%) and 1761 (62%) patients respectively. From 1991, over 80% of the postmenopausal, lymph node positive patients had received tamoxifen, irrespective of the steroid receptor status. Of all lymph node negative patients fewer than 3% received adjuvant systemic treatment. Among the lymph node negative patients the steroid receptor status was not a significant predictor of survival. Among the lymph node positive patients whose tumours were both ER-negative and PgR-negative, a 2.8-fold increased risk of death was found during the first four years after primary treatment. The risk of death was not increased if only the ER or only the PgR status was negative. CONCLUSION: This study shows that ER and PgR receptors are significant prognostic factors for survival in breast cancer patients with involved axillary lymph nodes. The prognostic effect appeared to be restricted to the first four years after primary treatment. Selection of patients for endocrine treatment should be based on the steroid receptor status, considering the importance of the steroid receptors for predicting the response to endocrine treatment.     

The value of pre-operative lymphoscintigraphy in breast cancer treatment

Three patients (aged 68-75 years) with histologically confirmed relapsed or refractory high-grade non-Hodgkin's lymphoma were entered in this pilot study in which gemcitabine 800 mg/m2 was given as a 30 min i.v. infusion once a week for 3 weeks. One patient responded with complete remission and the other two with partial remission and stable disease for 2 and 3 months, respectively. Haematological toxicity was modest with grade 4 leucopenia (one cycle) and grade 4 thrombocytopenia (two cycles). The activity and mild toxicity seen with gemcitabine suggest that this agent should be further evaluated in the treatment of high-grade non-Hodgkin's lymphoma.     

Radiotherapy and local control in rectal cancer

Recurrence is a stage in the natural history of rectal cancer. Preoperative radiotherapy or postoperative radiochemotherapy lower the rate of recurrence, improving local control. From 1980 to 1997, at the "Divisione di Radioterapia" of the "Università Cattolica del S. Cuore" of Rome 380 patients with rectal cancer of early clinical stage T2-3, candidates for surgery for cure, underwent radiation therapy. 119 patients underwent postoperative radiotherapy (45-50 Gy); 45 patients underwent "sandwich" radiotherapy (45 Gy:27 Gy before and 28 Gy after surgery), of whom 7 were treated with preoperative radiotherapy alone; 145 patients underwent preoperative concomitant radiochemotherapy according to 3 different protocols, radiotherapy (38 Gy) combined with mitomycin C and 5-FU; radiotherapy (50.4 Gy) combined with cisplatin and 5-FU; radiotherapy (45 Gy) combined with 5-FU and folinic acid. 71 patients were treated with preoperative radiotherapy (38 Gy) combined with IORT (10 Gy). Median follow-up was 6 years. Overall local control was 85% at 3 years, 83% at 5 years, 81% at 10 years. The rate of local control at 5 years was: 76% for postoperative radiotherapy, 83% for "sandwich" radiotherapy, 84% for preoperative radiochemotherapy and 93% for preoperative radiotherapy combined with IORT. Local control was shown to be significantly better with preoperative treatment as compared to postoperative treatment (p = 0.02). The incidence of metastases was 35% in the patients with local recurrence and 16% in those with local control. The difference in survival was highly significant in patients with local control as compared to those with local recurrence: at 5 years 87% and 32% respectively. Patients with local control showed a lower incidence of metastasis and a better survival.     

The link between local recurrence and distant metastases in human breast cancer

PURPOSE: To distinguish between two possible explanations for the increased incidence of distant metastases observed in patients with locoregional recurrences (LR). Either LR is the signature of tumor aggressiveness, and avoiding recurrences (i.e., by radiotherapy) is of little value. The alternative is that LR is a nidus for metastatic dissemination. METHODS AND MATERIALS: Four thousand patients consecutively treated in the same institution from 1954 to 1975 were studied. None of them had received adjuvant chemotherapy. Tumor characteristics, local recurrence, and distant metastases had been prospectively registered. Duration of metastatic growth and probability of metastatic dissemination were estimated in the subsets of patients. RESULTS: The proportion of metastasis-free patients was reduced by about 80% in all subsets of patients with LR. In patients without LR, the monthly rate of distant metastases incidence decreases continuously with time after initial treatment. Conversely, in patients with local recurrence, this rate increases during the first year at initial treatment and the metastases in excess appear slightly later than in patients without local recurrence. Using a mathematical model, it can be shown that, in patients with local recurrence, nearly all of the metastases in excess had been initiated after initial treatment. The data also suggest that each year a small proportion of grade 1 residual tumors progresses toward a more malignant histologic type. CONCLUSIONS: Our results are not consistent with the hypothesis that a greater tumor aggressiveness in patients with LR could explain the excess of metastases. This conclusion is supported by the analysis of the delays between metastases' emergence, and death, which shows that tumors with or without LR have similar biological characteristics.     

The surgical management of breast cancer, especially breast conserving treatment

The management of breast cancer is highly controversial. Various operations have been performed at different hospitals. Herein, we reviewed the results of randomized clinical trials regarding breast conserving treatment, and axillary and internal mammary lymph node dissections. Variations in local-regional therapy may not substantially affect survival, but the incidence of local-regional failure is inversely related to the extent of operation and/or radiotherapy. At present, surgeons are highly recommended to perform adequate surgery which provides the ultimate local control, does not compromise the chance for cure and gives the best cosmetic and aesthetic results. Therefore, quadrantectomy with or without immediate reconstruction, axillary dissection and internal mammary biopsy and breast irradiation are more preferably recommended for ensuring local control and for providing a better cosmetic and psychological impact.     

The potential role of somatostatin analogues in breast cancer treatment

Existing treatments for breast cancer are helpful for many patients, but treatment failure remains a common event, and there is a strong clinical need to improve upon current therapies. Somatostatin analogues have been evaluated for antineoplastic activity in model systems over the past decade, and encouraging results have been obtained (reviewed in [1, 2]). This has led to suggestions to test these agents clinically in the treatment of breast cancer patients, and a program of clinical trials has recently been initiated. This review will describe aspects of research in this area.     

Value of reduction mammoplasty in the conservative treatment of breast neoplasms. Apropos of 70 cases

Breast cancer surgery is on the increase. Until now conservative treatment has been limited to tumors less than 3 cm; it is now extending to surgery on reduced tumors after chemotherapy or radiotherapy. Some cancers still require mastectomy because a carcinologic satisfactory tumorectomy would create a major deformity not compatible with conservative treatment. It is technically possible to perform major tumor resection with good cosmetic results using the reduction mammoplasty technique well known in plastic surgery. Between 1983 and 1991, 70 patients were treated at Henri Mondor Hospital for breast cancer with breast reduction mammoplasty and irradiation. We present the result with an average five years follow-up in terms of the cosmetic results relapses and survival rate. The actuarial local relapse was less than 10%, the survival with local relapse was 86% after 5 years, cosmetic results were good in 81% of cases. The association of reduction mammoplasty and radiotherapy seems to be a good extension of conservative treatment in some large breast tumors.