Early-stage bilateral breast cancer treated with breast-conserving surgery and definitive irradiation: the University of Pennsylvania experience

PURPOSE: To determine whether patients with early-stage bilateral breast cancer can be treated with definitive irradiation following breast-conserving surgery with acceptable survival, local control, complications, and cosmesis. METHODS AND MATERIALS: During the period 1977-1992, 55 women with Stage 0, I, or II concurrent (n = 12) or sequential (n = 43) bilateral breast cancer were treated with definitive irradiation following breast-conserving surgery. The records of these 55 patients with 110 treated breasts were reviewed for tumor size, histology, pathologic axillary lymph node status, first and overall site(s) of failure, and adjuvant chemotherapy or hormonal therapy. Curves for survival, local control, and regional control were determined. Cosmetic outcome, complication rates, and matching technique were analyzed. The median total radiation dose delivered was 64 Gy (range 42-72) using tangential whole-breast irradiation followed by an electron or iridium implant boost. The tangential fields were matched with no overlap in 40 patients (73%); there was overlap on skin of up to 4 cm in 14 patients (25%); and the matching technique was unknown in 1 patient (2%). The median follow-up for the 12 women with concurrent bilateral breast cancer was 4.0 years. The median follow-up for the other 43 women with sequential cancer was 9.3 and 4.9 years, respectively, after the first and second cancers. RESULTS: For the overall group of 55 patients, the 5- and 10-year overall survival rates were 96% and 94%, respectively, after treatment of the first cancer, and 96% and 92%, respectively, after treatment of the second cancer. The 5- and 10-year actuarial relapse-free survival rates were 90% and 75%, respectively, after treatment of the first cancer, and 83% and 72%, respectively, after treatment of the second cancer. For the 110 treated breast cancers, the 5- and 10-year actuarial local failure rates were 5% and 15%, respectively. Complication rates were: 28% breast edema, 8% arm edema, 4% pneumonitis, 3% cellulitis, 1% rib fracture, and 1% brachial plexopathy; no patient developed matchline fibrosis. For patients with a minimum of 3 years of relapse-free follow-up, the rate of excellent or good cosmetic outcome for 104 treated breasts was 85%. CONCLUSION: Definitive irradiation after breast-conserving surgery is technically feasible for selected patients with concurrent or sequential early-stage bilateral breast cancer. Survival, local control, complication rates, and cosmetic outcomes appear comparable to historical reports of breast conservation treatment for unilateral disease. Bilateral definitive breast irradiation after breast-conservation surgery should be considered an acceptable alternative treatment to bilateral mastectomy for selected patients with concurrent or sequential early-stage bilateral breast cancer.     

Pattern of failure in patients with inflammatory breast cancer treated by alternating radiotherapy and chemotherapy

BACKGROUND: Patients with inflammatory breast cancer have a high risk of developing a local recurrence and/or distant metastases. Treatment with combined chemotherapy and locoregional radiotherapy contributes to a decrease in both risks. This study presents treatment results and evaluates the pattern of failure when an alternating chemoradiotherapy schedule is used. METHODS: One hundred twenty-five patients with nonmetastatic inflammatory breast cancer were treated with an alternating schedule of radiotherapy and chemotherapy. All women recruited were younger than 70 years of age and had a T4d, histologically proven infiltrating carcinoma with N0 to N2 axillary disease. The protocol consisted of three cycles of induction chemotherapy with doxorubicin, vincristine, cyclophosphamide, methotrexate, and 5-fluorouracil followed by three series of locoregional radiotherapy, delivering a total dose of 65-75 Gy to the breast tumor. Five additional cycles of chemotherapy with 5-fluorouracil/doxorubicin/cyclophosphamide were to be administered in between the first two and after the third radiotherapy course. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. RESULTS: Toxicity was moderate and this strategy proved feasible although most of the patients only received six instead of the eight planned cycles of chemotherapy. Eighty-two percent of the patients achieved a complete response at the end of the treatment. The cumulative 5-year local failure and distant metastasis rates were 27% and 53%, respectively. Assuming competing events, local failures, contralateral recurrences, and distant metastases were the first site of failure in 18%, 5%, and 38% of patients, respectively. The 5-year overall and disease free survival rates were 50% and 38%, respectively. The main prognostic factor was tumor size. CONCLUSIONS: Alternating high doses of radiotherapy and chemotherapy is a feasible treatment schedule and permits breast conservation. Disease free survival is comparable to that of recently published series. As the main causes of failure are distant metastases, higher dose chemotherapy should be evaluated, in an attempt to further improve overall survival.     

Recurrence and survival analyses of 1,115 cervical cancer patients treated with radical hysterectomy

Embryonal rhabdomyosarcoma is the most common malignant soft-tissue tumor in childhood. Cytogenetic studies of this tumor are rare. In one study trisomy 8 was found to be a primary cytogenetic abnormality. In view of the findings of trisomy 8 in a multitude of cancers, we conducted a pilot study to test the hypothesis that a subset of rhabdomyosarcoma also exists with trisomy 8. Accordingly, archival tissues of 12 cases of rhabdomyosarcoma were retrieved and fluorescence in situ hybridization (FISH) using a chromosome 8-specific, alpha-satellite probe was undertaken on formalin-fixed paraffin-embedded tissue sections using the protocol optimized in the Cytogenetics Laboratory at Rhode Island Hospital. The results obtained demonstrated that 6 of 12 tumors showed chromosome 8 trisomy, when a 15% threshold is adopted. In addition, one case was borderline, with 11% of the cells found positive for three fluorescent signals. Future experiments utilizing additional specimens from our centers as well as from other laboratories are needed to confirm and extend the findings of the present study.     

Cytomegalovirus papillitis in patients with acquired immune deficiency syndrome. Visual prognosis of patients treated with ganciclovir and/or foscarnet

BACKGROUND: Of those patients with acquired immune deficiency syndrome in whom cytomegaloviral retinitis develops, cytomegaloviral papillitis reportedly develops in up to 4% as well. Although occasionally patients have a good visual outcome, the majority have a poor visual prognosis, with a visual acuity of 20/200 or worse, even with treatment. METHODS: To evaluate the effects of prolonged induction with foscarnet or ganciclovir on the visual prognosis of cytomegalovirus (CMV) papillitis, the records of 22 patients seen between 1990 and 1995 at the Los Angeles County-University of Southern California Eye Clinic were reviewed. Papillitis was defined as greater than 270 degrees of disc edema/blurring of the disc margins as seen on direct examination and on color fundus photographs. RESULTS: Eighteen patients with a mean initial visual acuity of 20/69 (range, 20/ 15-20/400) were treated with induction doses of intravenous ganciclovir (range, 5-7.5 mg/kg twice daily) or foscarnet (range, 60-90 mg/kg twice or 3 times daily) for a mean of 3.3 weeks. The mean follow-up period was 4.8 months (range, 1-13 months). These patients maintained a mean final visual acuity of 20/68 (range, 20/ 25-20/400) with greater than 90% resolution of the papillitis. The remaining four patients had poor outcomes (visual acuity < 20/400) because of progressive CMV papillitis or retinitis. The median survival time was 4.5 months from the diagnosis of papillitis, but 7 months from the onset of CMV ocular infection. CONCLUSION: Patients with CMV papillitis have good visual prognosis when managed with high and prolonged doses of intravenous foscarnet and/or ganciclovir.     

Epidemiologic and etiologic factors in cancer of the breast. Catamnestic investigations on 749 patients of the Department of Radiology at Essen (author's transl)

Morbidity- and morality statistics of cancer of the breast show a clear increase in almost all countries. The numbers of patients who died increased particularly in countries situated around the north-sea. It appears that unmarried women run a greater risk, as reported by many authors. On further risks we could not confirm that those women with few children predominated. Our results correspond to numbers calculated for abortions. More children increase the danger of breast cancer. These evaluations cannot be separated from the impact of shortened breast-feeding and sociologic factors which also influence the risk in an ill-defined manner. Breast-cancer is doubly to five times as common in female relatives of patients as shown in Anglo-american and our own materials. Age distribution among 742 patients shows, rather like that of some Scandinavian authors, peaks between 45 and 49 and between 56 and 63 years. This again raises the question of a post-menopausal stimulus. In our material there is an average delary of 4 1/2 months between first symptoms and start of treatment. The causes arise both from patients and doctors and, age apart, are responsible for the undue delay. Delay, invasion of lymph nodes and size of tumor establish a correlation between delay and stage of tumor. As to the site of the tomor the left breast was more often involved than the right in our patients. The upper lateral quadrant predominated. To extend the period of survival we shall have to reduce delay and develop further special techniques of treatment.     

Apgar status, blood gases and acid base balance of neonates after caesarean sections, using either thiopentone or ketamine for induction of anaesthesia (author's transl)

Apgar status and acid base balance of 206 neonates, delivered by caesarean section under general anaesthesia, were investigated in order to compare the possible effects of either thiopentone- or ketamine-induction on the postpartum adaption. Several other criteria were recorded also, for instance, a possible neonatal asphyxia, the induction-delivery-interval, the maternal age, the administration of other than anaesthetic drugs etc. There were not correlations between the Apgar status and the induction-delivery interval in either groups. The number of neonates within the 3 Apgar-classes, and the asphyxiated neonates, were equally distributed in the thiopentone- and ketamine-groups. There was no correlation between maternal ages and either the thiopentone- or ketamin-babies, but a marked correlation with the number of depressed newborns. Those neonates, who were suspected to be hypoxic before anaesthesia showed a more depressed post-partum respiration after thiopentone- than after ketamine-induction. On the other hand it seems to be that neonatal respiration and total Apgar status was more depressed if the "ketamin mothers" were treated with sedatives, hypnotics and/or analgesics before caesarean section. The blood gas values and the acid base parameters did not show a statistically significant difference between the pH of the thiopentone- and the ketamine-neonates. These differences can be explained as the combination of the nonsignificant changes in PCO2 and standard-bicarbonate values. As far as can be judged from the above mentioned criteria it may be deduced that ketamine or thiopentone can equally well be used for inducation of anaesthesia for caesarean section.     

The intracorporeal ultraviolet irradiation of the blood and its effect on the immune status in patients with a surgical infection

A dynamic investigation was done of the immunologic status in 75 patients with purulent surgical lesions of soft tissues. Applied in the complex of therapeutic measures was intracorporeal irradiation of blood with ultraviolet light under control of partial pressure of oxygen and carbon dioxide. The above irradiation was found out to make for a more rapid and marked stabilization of bodily immunologic status.     

Studies on antigenic relationship between grass- and cult. rye pollens by skin-test, RAST and RAST-inhibition-test in patients with pollinosis (author's transl)

Skin tests on patients suffering from pollinosis suggest frequently an antigenic relationship between various grass and cult. rye pollens. This problem was further studied using both, RAST and RAST inhibition test. The tests were performed with commercial grass pollen discs as well as with self-prepared disc labeled with cult. rye pollens and a combination of various grass antigens. Good agreement was found between self-made and commercial (single antigen) grass pollen discs (95.9%). RAST and skin test correlated also extremely well (92.3%). Mutual inhibition between grass and cult. rye pollens was measured by RAST inhibition test using self-prepared discs. High antigenic relationship between grass and cult. rye pollens was found, however, it could be demonstrated that the antibody pattern varies and contains "grass specific" antibodies.     

Treatment of malignant and premalignant diseases of the breast by subcutaneous mastectomy with simultaneous augmentation mammoplasty (author's transl)

Among 6 patients with small intra-ductal carcinomas of the breast two had local recurrences of cancer following unilateral subcutaneous mastectomy. We therefore limit subcutaneous mastectomy to pre-cancerous conditions and then use a bilateral subcutaneous mastectomy with augmentation mammoplasty. Our methods and results in 28 cases are described. We think that the removal of approximately 95% of the breast tissue is enough assurance to the patient that no cancer will develop later. The patients are happy with the cosmetic results and abandon their cancerophobia generated by long term diagnostic observation.     

Studies on cell-mediated immune responses by human lymphocytes in vitro. III. Lymphocyte response to phytohemagglutinin and concanavalin A in patients with auto-immune diseases

A study was undertaken concerning prevalence of psychic disorders among 175-5 to 6-year-old, pre-school children randomly selected from the general population in the municipality of Aarhus and the island Sams? of Aarhus County, Denmark. Deviant behaviour was arbitrarily defined, with a symptom considered aberrant if it occurred in 10% or less of the children studied. Mental health of the children was assessed by (a) the number of deviant symptoms, (b) opinions of the parents and (c) the personal assessment of the author, who interviewed all the families. Thirty-five probands (20%) showed good adjustment, 113 (65%) were coping well with only minor symptoms, and 27 children (15%) were poorly adjusted. A high prevalence of psychosomatic, behavioural, and emotional symptoms was observed, some of them more frequently among boys than girls. No significant difference was found between urban and rural children. The need for psychiatric help even among supposedly normal, pre-school children is discussed and emphasized.     

Control of emesis by intravenous granisetron in breast cancer patients treated with 5-FU, epirubicin and cyclophosphamide

Granisetron, a potent and selective 5-hydroxytryptamine receptor (5-HT3) antagonist was reported to be an effective antiemetic agent both in animal studies and in patients given highly emetogenic chemotherapy. A sample of 43 patients with breast cancer was accrued from September to November 1992 in a phase II study to assess the efficacy of granisetron in patients receiving FEC (5-FU, epirubicin, cyclophosphamide). Each patient received 3 mg intravenous granisetron as a single dose just prior to chemotherapy. Oral metoclopromide was prescribed to each patient as a rescue anti-emetic. The emetic episodes and degree of nausea were evaluated on a daily basis. Good control of emesis (0-2 episodes of vomiting) and nausea (mild or no nausea) was in the range 77%-98% and 77%-93% respectively. There was a complete response (no emetic episodes throughout the 6-day period) in 16 patients (37.2%). Onset of emesis tends to occur on day 1 and tend to subside after day 3; 85% of patients had onset of emesis in the first 2 days after chemotherapy. Control of emesis and nausea tends to improve after day 3, which could be the result of the reduced emetogenicity of the combination FEC with time. Altogether, 77% had good control of acute emesis; control of delayed emesis was better with 84% achieving a major response on day 2 after chemotherapy, which improved to more than 90% after day 4. Granisetron was generally tolerated with headache being the most common side-effect followed by constipation and flushing. This study suggests that granisetron is an effective and well-tolerated anti-emetic agent, which deserves randomised trials to elucidate its efficacy further.