NCI CANCERLIT^® Search: Radiotherapy for Breast Cancer - September 2001

Last Modified: November 1, 2001

A cost-outcome analysis of adjuvant postmastectomy locoregional radiotherapy in high-risk postmenopausal breast cancer patients.
The response of human breast tumour cell lines with altered polymerase beta levels to cisplatin and radiation.
Time trends in the results of breast conservation in 4694 women.
Adjuvant therapy for breast cancer.
Systemic radiotherapy in metastatic breast cancer using 90Y-linked monoclonal MUC-1 antibodies.
Partial irradiation of the heart.
[Diagnostic image (46). Post-radiation angiosarcoma of the breast]
Do surgical oncologists achieve lower rates of local-regional recurrence in node positive breast cancer treated with mastectomy alone?
Psoriasis and radiotherapy: exacerbation of psoriasis following radiotherapy for carcinoma of the breast (the Koebner phenomenon).
Bullous skin disorders following radiotherapy.
Impact of chemotherapy dose-density on radiotherapy dose-intensity after breast conserving surgery.
Multifocal squamous cell carcinoma of the oesophagus following radiotherapy for bilateral breast carcinoma.
Psoriasis and radiotherapy.
Phase II study assessing the effectiveness of Biafine cream as a prophylactic agent for radiation-induced acute skin toxicity to the breast in women undergoing radiotherapy with concomitant CMF chemotherapy.

CancerMail from the National Cancer Institute

1
UI - 21394553
AU - Samant R; Dunscombe P; Roberts G
TI - A cost-outcome analysis of adjuvant postmastectomy locoregional radiotherapy in high-risk postmenopausal breast cancer patients.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1376

2
UI - 21388261
AU - Raaphorst GP; Cybulski SE; Sobol R; Ng CE
TI - The response of human breast tumour cell lines with altered polymerase beta levels to cisplatin and radiation.
SO - Anticancer Res 2001 May-Jun;21(3B):2079-83
AD - ORCC, Ottawa, Ontario, Canada.
MCF 7 (human breast carcinoma cells) and mutants transfected with the DNA polymerase beta gene were tested for response to cisplatin, radiation and combined treatments. The transfected cells showed a higher level of polymerase beta activity and were more resistant to radiation and cisplatin compared to the parental cell line. Further studies showed that for isosurvival treatments the mutant cells were more effective in sublethal radiation damage repair compared to the parental line. The combination of cisplatin with radiation showed effective radiosensitization which was less in the mutants compared to the parental line. In addition, the sequence of cisplatin before irradiation was more effective then cisplabn after irradiation. Pre-exposure to low levels of cisplatin for up to 24 h before irradiation showed a small significant adaptive response in one mutant line at 8 h and while similar trends were observed in the parental lines at earlier times they were not significant. In summary our data show that polymerase beta and thus base excision repair may play a role in cellular responses to cisplatin and radiation.

3
UI - 21398078
AU - Fredriksson I; Liljegren G; Arnesson LG; Emdin SO; Palm-Sjovall M; Fornander T; Frisell J; Holmberg L
TI - Time trends in the results of breast conservation in 4694 women.
SO - Eur J Cancer 2001 Aug;37(12):1537-44
AD - The Karolinska Institute, Department of Surgery, Stockholm Soder Hospital, Stockholm, Sweden. irma.fredriksson@kirurg.sos.sll.se
In a population-based cohort of 4694 women with invasive breast cancer, operated upon with breast conserving surgery (BCS) in 1981--1990 and followed through to 1997, we studied how this technique had been adopted into clinical practice, especially with reference to the use of radiotherapy (RT). Our main aim was to see whether there was a drift in the risk of local recurrence and breast cancer death over time. During the 30,151 person-years of observation in the cohort, there were 582 local recurrences, 456 breast cancer deaths and 438 deaths due to other causes. Postoperative RT was given to 70.2%, but usage increased over the period. The women not receiving RT were mostly elderly, but also in women <70 years, 20.4% did not receive RT. The risk for local recurrence after RT were 7.6 and 17.8% at 5 and 10 years, respectively. Without RT, more than 30% had a local recurrence at 10 years. Thus, the choice not to irradiate failed to target women at a low risk. In a multivariate Cox analysis taking tumour size, nodal status, age at operation and RT into account, there was a trend for a higher risk of local recurrence in the later time period, relative hazard 1.5 (95% confidence interval (CI) 1.0--2.1). Corrected survival was 93.3 and 85.2% at 5 and 10 years, respectively.

4
UI - 21404773
AU - Anonymous
TI - Adjuvant therapy for breast cancer.
SO - NIH Consens Statement 2000 Nov 1-3;17(4):1-35
OBJECTIVE: To provide health care providers, patients, and the general public with a current consensus on various issues related to the use of adjuvant therapy for breast cancer. PARTICIPANTS: A nonfederal, nonadvocate, 14-member panel representing the fields of oncology, radiology, surgery, pathology, statistics, public health, health policy, and the public; 30 experts in medical oncology, molecular oncology, biostatistics, epidemiology, surgical oncology, and clinical trials who presented data to the consensus panel; a conference audience of approximately 1,000. EVIDENCE: The literature was searched using MEDLINE and an extensive bibliography of references was provided to the panel. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately following its release at the conference and was updated with the panel's final revisions. CONCLUSIONS: During the past 10 years, substantial progress has been made in the treatment of invasive breast cancer. For the first time, breast cancer mortality rates are decreasing in the United States. Refinements of adjuvant treatment have contributed to this advance. Generally accepted prognostic and predictive factors include age, tumor size, lymph node status, histological tumor type, grade, mitotic rate, and hormonal receptor status. Novel technologies, such as tissue and expression microarrays and proteomics, hold exciting potential. Progress, however, will depend on proper design and analysis of clinical and pathological investigations. Decisions regarding adjuvant hormonal therapy should be based on the presence of hormone receptor protein in tumor tissues. Adjuvant hormonal therapy should be offered only to women whose tumors express hormone receptor protein. Because adjuvant polychemotherapy improves survival, it should be recommended to the majority of women with localized breast cancer regardless of nodal, menopausal, or hormone receptor status. The inclusion of anthracyclines in adjuvant chemotherapy regimens produces a small but statistically significant improvement in survival over non-anthracycline-containing regimens. Available data are currently inconclusive regarding the use of taxanes in adjuvant treatment of node-positive breast cancer. The use of adjuvant dose-intensive chemotherapy regimens in high-risk breast cancer and of taxanes in node-negative breast cancer should be restricted to randomized trials. Ongoing studies evaluating these treatment strategies should be supported to determine if they have a role in adjuvant treatment. Studies to date have included few patients older than 70 years. There is a critical need for trials to evaluate the role of adjuvant chemotherapy in these women. There is evidence that women with a high risk of locoregional tumor recurrence after mastectomy benefit from postoperative radiotherapy. This high-risk group includes women with four or more positive lymph nodes or an advanced primary cancer. Currently, the role of post-mastectomy radiotherapy for patients with one to three positive lymph nodes remains uncertain and should be tested in a randomized controlled trial. Individual patients differ in the importance they place on the risks and benefits of adjuvant treatments. Quality-of-life needs to be evaluated in selected randomized clinical trials to examine the impact of the major acute and long-term side effects of adjuvant treatments, particularly premature menopause, weight gain, mild memory loss, and fatigue. Methods to support shared decision-making between patients and their physicians have been successful in trials; they need to be tailored for diverse populations and should be tested for broader dissemination.

5
UI - 21152855
AU - Richman CM; DeNardo SJ
TI - Systemic radiotherapy in metastatic breast cancer using 90Y-linked monoclonal MUC-1 antibodies.
SO - Crit Rev Oncol Hematol 2001 Apr;38(1):25-35
AD - University of California-Davis, School of Medicine, Division of Hematology/Oncology, 4501 X Street, Sacramento, CA 95817, USA. carol.richman@ucdmc.ucdavis.edu
Radioimmunotherapy (RIT) is a promising approach for treating metastatic breast cancer. Initial clinical trials using 131I radioimmunoconjugates, and more recent studies employing 90Y, have demonstrated objective, although transient, antitumor effects in heavily pretreated patients with minimal toxicity. Antibodies targeting unique epitopes of epithelial glycoprotein mucin (MUC-1) on breast cancer cell surfaces that have been studied in patients include BrE-3 (murine and humanized) and m170 (murine). Both antibodies react with at least 90% of breast cancers. In these and other RIT trials, myelosuppression has been the dose-limiting toxicity. However, this toxicity has been successfully circumvented with the use of autologous peripheral blood stem cell transplantation, and recent clinical trials have escalated 90Y doses up to 50 mCi/m(2). The therapeutic index indicates that using these agents with stem cell support should deliver 9000 to 18000 rads to metastatic tumors. Development of improved chelates that are readily metabolized in the liver may reduce doses to this organ, projected to be next in line as dose-limiting. Combination therapy will be required to produce durable benefits in metastatic breast cancer. Low dose taxanes are synergistic with RIT in preclinical studies and when administered in the optimal sequence could sensitize tumor cells to the continuous low dose radiation delivered by RIT, without increasing toxicity. The addition of systemically administered tumor targeting radiation therapy using RIT as part of combined modality therapy may enhance the rate of complete response and, in patients with minimal metastatic disease, could lead to curative therapy.

6
UI - 21340752
AU - Gagliardi G; Lax I; Rutqvist LE
TI - Partial irradiation of the heart.
SO - Semin Radiat Oncol 2001 Jul;11(3):224-33
AD - Department of Hospital Physics, Radiumhemmet, Karolinska Hospital, 171 76 Stockholm, Sweden. giovanna.gagliardi@ks.se
Radiation-induced heart disease (RIHD) includes pericarditis, ischemic heart disease, and myocardial infarction and leads in some cases to fatal complications. It has been shown that the increased survival due to radiotherapy could be negated by excess deaths from RIHD in breast cancer radiotherapy for left-sided tumors. Subclinical effects following irradiation have been detected in several studies both of breast cancer and Hodgkin's irradiation. The dose-volume response relationships describing cardiac complications have been studied for pericarditis and cardiac mortality by means of biologic models, including the well-known Lyman-Kutcher-Burman (LKB) model and Kallman's relative seriality model. Studies by Martel and coworkers on pericarditis and by Gagliardi and coworkers on cardiac mortality are reviewed. The anatomical and functional definition of the heart represents a key issue in modeling, as it affects strongly the dosimetrical data to be used as input data in the models. Several treatment strategies to decrease heart irradiation, based on models and/or based on dose-distribution evaluations, are reviewed. It is concluded that left-sided breast cancer patients should always be 3-dimensional (3D) dose planned. Copyright 2001 by W.B. Saunders Company

7
UI - 21377736
AU - den Bakker MA; Baartman EA; van Geel AN
TI - [Diagnostic image (46). Post-radiation angiosarcoma of the breast]
SO - Ned Tijdschr Geneeskd 2001 Jul 14;145(28):1351
AD - Afd. Pathologie, Academisch Ziekenhuis Rotterdam-Daniel den Hoed Kliniek, Postbus 5201, 3008 AE Rotterdam.
A 71-year-old woman developed an angiosarcoma of the breast, five years after an adenocarcinoma had been removed and additional local radiation therapy with 70 Gy had been given.

8
UI - 21410077
AU - Latosinsky S; Bear HD
TI - Do surgical oncologists achieve lower rates of local-regional recurrence in node positive breast cancer treated with mastectomy alone?
SO - J Surg Oncol 2001 Sep;78(1):2-7; discussion 8-9
AD - Department of Surgery, Division of Surgical Oncology, University of Manitoba, Winnipeg, Manitoba, Canada.
BACKGROUND AND OBJECTIVE: Adjuvant radiotherapy for node positive breast cancer postmastectomy has been recommended by two previously published randomized controlled trials (RCT). The local-regional recurrence rates in the control arms, however, were considered by some critics to be excessive (> 25% at 10 years). Inadequate surgery, as evidenced by the low number of axillary nodes reported, may have resulted in the high local-regional recurrence rates, allowing for the benefits seen with radiotherapy. Fellowship trained surgical oncologists might provide "better quality" surgery, resulting in lower recurrence rates and thus making adjuvant radiotherapy unnecessary. Our objective was to establish the local-regional control rate postmastectomy in node positive breast cancer patients operated on by surgical oncologists, and to determine if treatment recommendations from previous RCTs are generalizable. METHODS: Node positive stage IIb and IIIa breast cancer patients treated with mastectomy at the Medical College of Virginia Hospitals by surgical oncologists, without adjuvant radiotherapy, and entered into adjuvant chemotherapy trials between 1978 and 1993 were identified retrospectively. Pathology and follow-up records were reviewed. RESULTS: One hundred and thirty-seven patients were identified. A median of 18 axillary nodes was reported with a median of 4 positive nodes. The locoregional recurrence at 10-years was 27% (95% confidence interval, 19-35%). CONCLUSION: Despite some evidence of "better quality" surgery, there was no clinically significant difference in the local-regional recurrence rate in this case series compared to controls in two previous RCTs. Recommendations for postmastectomy radiotherapy should be considered for node positive breast cancers, even if operated upon by surgical oncologists. Copyright 2001 Wiley-Liss, Inc.

9
UI - 20395786
AU - Charalambous H; Bloomfield D
TI - Psoriasis and radiotherapy: exacerbation of psoriasis following radiotherapy for carcinoma of the breast (the Koebner phenomenon).
SO - Clin Oncol (R Coll Radiol) 2000;12(3):192-3
AD - Sussex Oncology Centre, Royal Sussex County Hospital, Brighton, UK.
We report the case history of a patient with a known history of psoriasis, who developed an exacerbation of the treated skin area after radiotherapy for carcinoma of the breast. This illustrates the Koebner phenomenon, with the replication of a dermatosis at the site of skin trauma.

10
UI - 21212318
AU - Hartley A; Agrawal R
TI - Bullous skin disorders following radiotherapy.
SO - Clin Oncol (R Coll Radiol) 2000;12(5):336-7

11
UI - 21230833
AU - Sanguineti G; Del Mastro L; Guenzi M; Ricci P; Cavallari M; Canavese G; Stevani I; Venturini M
TI - Impact of chemotherapy dose-density on radiotherapy dose-intensity after breast conserving surgery.
SO - Ann Oncol 2001 Mar;12(3):373-8
AD - Department of Radiation Oncology, National Cancer Research Institute of Genoa, Italy.
PURPOSE: To evaluate if chemotherapy (CT) dose-intensification jeopardizes radiotherapy (RT) dose-intensity (DI). PATIENTS AND METHODS: From 1992 to 1997, 247 stage I-II breast cancer patients, treated with conserving surgery, were treated at the National Cancer Institute of Genoa in a randomized study comparing the same CEF regimen delivered every two weeks (CEF14) or three weeks (CEF21). RT was applied to the residual breast at a total dose of 50 Gy in five weeks. Allowance was made for treatment at 2.3 Gy per fraction in order to compensate for gaps (hypofractionation). Radiotherapy DI was expressed as the average total dose received each week, i.e., 'weekly dose-rate' (WDR). The effect of various tumour, treatment and patient-related factors on the endpoint (a delivered WDR of RT < 9.5 Gy) was investigated by univariate analysis. Factors found to have P-value < or = 0.20 were entered in multivariate analysis. RESULTS: All but three patients (244 of 247, 98.8%) received a cumulative total dose of RT within +/- 10% of that planned. Moreover, most of them (197 of 247, 79.8%) received an average WDR of > or = 9.5 Gy/wk. With univariate analysis the probability of WDR < 9.5 Gy/wk significantly correlated with age, menopausal status, concomitant administration of RT and CT, and white blood cell toxicity. Moreover, a positive effect on WDR was found in patients treated at 2.3 Gy per fraction. The type of treatment (CEF14 vs. CEF21) did not affect the probability of WDR < 9.5 Gy/wk. With multivariate analysis, age (< or = 55 vs. > 55 years, RR = 3.99, 95% CI: 1.89-8.42, P = 0.0003), RT fractionation (conventional vs. hypofractionation, RR = 0.32, 95% CI: 0.15-0.68, P = 0.017) and WBC toxicity (none vs. some, RR = 1.54, 95% CI: 1.06-2.22, P = 0.027) were independent predictors of WDR < 9.5 Gy. Regarding the CT-RT overlap, patients receiving more than two cycles of chemotherapy during radiotherapy had an increased risk of RT delay compared to other patients (RR = 3.74, 95% CI: 1.44-9.48, P = 0.0063). CONCLUSIONS: There is no evidence of a direct effect of CT dose-density on dose-intensity of RT. However, the concomitant use of CT and RT reduces the possibility of giving a full dose-intensity of RT.

12
UI - 21424090
AU - Shousha S; Fawcett A; Luqmani YA; Theodorou N
TI - Multifocal squamous cell carcinoma of the oesophagus following radiotherapy for bilateral breast carcinoma.
SO - J Clin Pathol 2001 Sep;54(9):718-20
AD - Department of Histopathology, Imperial College School of Medicine and Charing Cross Hospital, London W6 8RF, UK. s.shousha@ic.ac.uk
A 60 year old woman who presented with dysphagia and weight loss was found to have multiple foci of dysplasia and in situ and invasive squamous cell carcinoma scattered along the whole length of the oesophagus, with intervening areas of normal mucosa. The patient had a history of two breast carcinomas 19 and one year previously for which she had repeated radiotherapy. Several members of the patient's close family had histories of malignant disease. All oesophageal lesions and the more recent breast cancer showed positive immunostaining for p53 protein. p53 mutations, some involving different exons, were also detected in these lesions. No p53 immunostaining or mutations were detected in the normal oesophageal mucosa. The findings suggest an independent origin of the multiple dysplastic and neoplastic foci, which might have developed in a background of a field change, possibly related to the previous radiotherapy. The strong family history of malignant diseases raises the possibility that, in addition, genetic factors might have played a role in the development of the oesophageal disease.

13
UI - 21447959
AU - Tomlinson MJ
TI - Psoriasis and radiotherapy.
SO - Clin Oncol (R Coll Radiol) 2001;13(2):145

14
UI - 21407952
AU - Szumacher E; Wighton A; Franssen E; Chow E; Tsao M; Ackerman I; Andersson L; Kim J; Wojcicka A; Ung Y; Sixel K; Hayter C
TI - Phase II study assessing the effectiveness of Biafine cream as a prophylactic agent for radiation-induced acute skin toxicity to the breast in women undergoing radiotherapy with concomitant CMF chemotherapy.
SO - Int J Radiat Oncol Biol Phys 2001 Sep 1;51(1):81-6
AD - Department of Radiation Oncology, Toronto-Sunnybrook Regional Cancer Centre, Sunnybrook and Women's College Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. ewa.szumacher@tsrcc.on.ca
PURPOSE: To assess the efficacy of Biafine cream in preventing Grade 2 acute radiation dermatitis, according to the National Cancer Institute of Canada skin radiation toxicity criteria in patients undergoing concomitant adjuvant chemotherapy and radiotherapy to the breast. METHODS AND MATERIALS: Sixty patients participated in this study. Patients were treated with a lumpectomy followed by concomitant chemotherapy and radiotherapy to the breast. Biafine cream was applied daily, starting on the first day and ending 2 weeks post-radiotherapy. Patients underwent weekly skin assessments throughout radiotherapy and at 2 and 4 weeks after treatment. Outcome measures were assessed using a Skin Assessment Questionnaire that was scored according to the National Cancer Institute of Canada skin radiation toxicity criteria and a self-administered questionnaire that evaluated skin symptoms. RESULTS: The maximum skin toxicity observed during the course of treatment was as follows: less than Grade 2 toxicity, 15% (9 patients); Grade 2, 83% (50 patients); Grade 3, 2% (1 patient); Grade 4, 0% (0 patients). The majority of the radiation dermatitis was observed after 3 weeks of radiotherapy. CONCLUSION: The majority of patients who underwent concomitant chemo- and radiotherapy for breast cancer developed Grade 2 radiation dermatitis with the use of Biafine cream. However, no treatment delays or interruptions were observed because of skin toxicity.