Ten years of breast screening in the Screening Mammography Program of British Columbia, 1988-97.

OBJECTIVES: To evaluate 10 years outcomes of the Screening Mammography Program of British Columbia (SMPBC) and determine if breast screening targets were being achieved among women aged 40-80+ years. SETTING: Organised breast screening programme in British Columbia, Canada. METHODS: Rates of participation, abnormal referral, cancer detection, and interval cancer were calculated for asymptomatic women receiving an SMPBC mammography from 1988-97. RESULTS: 895,849 screening mammographies were provided to 335,433 women. 51.3% of women were age 50-69 years. Abnormalities were identified on 57,454 screens (6.4%) from which 3304 cancers were detected. Abnormal call rates were higher on first (9.8%), compared with subsequent screens (4.4%) and declined with age: 7.7% at age < 40 to 5.4% for age 70-79 years. Cancer detection rates were higher on first (5.0 per 1000) compared with subsequent screens (2.8 per 1000) and increased smoothly with age from 1.4 to 8.2 per 1000 from age < 40 to age 80 years and older. Twenty per cent of cancers were non-invasive. The median size of invasive cancers was 14 mm and 81% had no axillary lymph node metastases. The 12 month interval cancer rate was 0.6 per 1000 and did not vary significantly with age or screening history. The prevalence to expected incidence ratio was 3.1 for women age 50-79 years. CONCLUSION: Across a broad range of ages, surrogate indices of screening mammography success have been achieved in a population based, North American, organised breast cancer screening programme.

Locoregional first recurrence after mastectomy: prospective cohort studies with and without immediate chemotherapy.

PURPOSE: To evaluate prospectively the impact of combination chemotherapy in the combined modality treatment of isolated first locoregional recurrence (LRR) following mastectomy for breast cancer. METHODS AND MATERIALS: Between 1979 and 1989, 120 chemotherapy-naive women with isolated LRR as first failure after mastectomy were prospectively identified, uniformly staged, and systematically followed. Treatment consisted of excision if feasible, radical locoregional radiotherapy, and a hormonal maneuver (unless estrogen receptor negative). The initial chemotherapy cohort also received 8 cycles of doxorubicin and cyclophosphamide. This was compared to a subsequent control cohort. RESULTS: For all patients, the 10-year actuarial relapse-free survival +/- 95% confidence interval was 42.1+/-9.2%, and overall survival was 56.8+/-9.1%. No difference was seen in locoregional control between cohorts. At 5 years, distant recurrence-free survival for chemotherapy and control cohort respectively was 75.4+/-10.8% and 60.7+/-12.5% (p = 0.33) and overall survival was 81.9%+/-9.6 and 74.3%+/-11.2 (p = 0.24). Univariate analysis showed no prognostic importance for any imbalance between cohorts. Cox modeling confirmed that complete resection was strongly associated with fewer LRR (hazard ratio [HR] 0.32, p = 0.001) and also with better overall survival (HR 1.82, p = 0.019). Chemotherapy produced a substantial reduction in risk of death (HR 0.72 CI 0.421-1.235, p = 0.23). CONCLUSIONS: In this prospective but nonrandomized study of treatment for first LRR, the risk of death in the later control cohort was 1.39 times the risk in the chemotherapy cohort but failed to reach statistical significance. The results justify further study.

Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer.

BACKGROUND: Radiotherapy after mastectomy to treat early breast cancer has been known since the 1940s to reduce rates of local relapse. However, the routine use of postoperative radiotherapy began to decline in the 1980s because it failed to improve overall survival. We prospectively tested the efficacy of combining radiotherapy with chemotherapy. METHODS: From 1978 through 1986, 318 premenopausal women with node-positive breast cancer were randomly assigned, after modified radical mastectomy, to receive chemotherapy plus radiotherapy or chemotherapy alone. Radiotherapy was given to the chest wall and locoregional lymph nodes between the fourth and fifth cycles of cyclophosphamide, methotrexate, and fluorouracil. RESULTS: After 15 years of follow-up, the women assigned to chemotherapy plus radiotherapy had a 33 percent reduction in the rate of recurrence (relative risk, 0.67; 95 percent confidence interval, 0.50 to 0.90) and a 29 percent reduction in mortality from breast cancer (relative risk, 0.71; 95 percent confidence interval, 0.51 to 0.99), as compared with the women treated with chemotherapy alone. CONCLUSIONS: Radiotherapy combined with chemotherapy after modified radical mastectomy decreases rates of locoregional and systemic relapse and reduces mortality from breast cancer.

Effect of acetylsalicylic acid on radiation and cosmetic results after conservative surgery for early breast cancer: a randomized trial.

BACKGROUND AND PURPOSE: Acetylsalicylic acid (ASA) can reduce the incidence of stroke and myocardial infarction by inhibiting platelet-fibrin thrombi in small blood vessels. To determine if ASA could reduce late effects of radiation therapy mediated by damage to small blood vessels, a prospective, placebo-controlled, double-blind trial was conducted in women with early breast cancer, receiving radiotherapy to the conserved breast. MATERIALS AND METHODS: Cosmetic outcome and late radiotherapy effects were recorded prospectively for 186 women with T1 or T2, pathologically node-negative breast cancer treated with breast conservation and randomized to receive ASA (325 mg daily) or placebo for 1 year from the start of radiation therapy. Radiation was a tangent pair to the breast alone delivering a modal dose of 44 Gy in 16 daily fractions in 22-25 days. RESULTS: Median follow-up is 6.5 years. The use of ASA has not had any effect on the acute (erythema, edema or discomfort) or late (induration, telangiectasia) effects of radiotherapy (all P > 0.10), the patients' or physicians' assessment of the cosmetic outcome (all P > 0.25) or rates of breast recurrence (P > 0.25). CONCLUSION: ASA cannot be recommended to improve the outcome of radiotherapy complementing breast conserving surgery.

Late cosmetic results of short fractionation for breast conservation.

BACKGROUND AND PURPOSE: The number of fractions of radiation therapy (RT) used after breast conserving surgery varies widely and accounts for a significant proportion of the workload in a modern radiotherapy department. Internationally, 'standard' therapy ranges from 3 to 7 weeks of daily treatment with or without a boost. Short RT schedules have the attraction of reducing workload but raise concern about an increased risk of late effects and poorer cosmetic outcome. MATERIALS AND METHODS: In a randomized trial, 186 women with T1 or T2, pathologically node-negative breast cancer had cosmetic and various normal tissue effects data collected prospectively. The breast RT prescription was 44 Gy in 16 daily fractions to a tangent pair. RESULTS: Median follow-up is 6.7 years. Actuarial 5-year breast recurrence was 6%. Overall cosmetic results at 5 years were good or excellent in 89% and 96% as reported by physicians and patients, respectively, and were stable between 2 and 5 years. Breast discomfort, erythema, edema and induration were related to both surgery and RT. At 5 years, 20% had breast discomfort, 18% had induration, 6% had erythema and 3% had some degree of breast edema. Fewer patients had these effects at 5 years than immediately after primary surgery. The presence of induration prior to starting RT was associated with a greater likelihood of breast induration 3 or more years following RT (P = 0.02). Thirteen percent of patients, generally those with large breasts, developed mild inframammary telangiectasia by 5 years. CONCLUSIONS: Results are comparable to those reported from centers employing more conventional fractionation. Short fractionation produces acceptable cosmetic results for the majority of women if there are no contraindications to RT and in the absence of significant post-operative breast induration.

Comparison of partial and modified radical mastectomy in the community setting--"10 years later".

Conservative surgery followed by postoperative radiation is considered equivalent to a modified radical mastectomy (MRM) for the treatment of early breast cancer. It cannot be assumed that results from selected academic centres are equivalent to those obtained in the general community setting, because there may be differences in patient selection or surgical or radiotherapy techniques that may adversely affect outcome. A quality-control study of women who were seen at the British Columbia Cancer Agency and were treated by partial mastectomy (PM) was begun in 1983. Eighty-four women who underwent conservative surgery between January 1979 and November 1982 and were referred to the British Columbia Cancer Agency were matched with 84 women who underwent MRM. The mean follow-up was 10.5 years. At 10 years disease-free survival in both groups was 63%. Survival overall for the PM group was 72.6% and for the MRM group was 69%. The survival rate decreased with increasing size of the tumour and increasing number of nodes. In women with lymph-node involvement there was a survival advantage for those treated by PM and radiation compared with those treated by MRM. The woman's age at diagnosis did not affect these findings. Recurrence and complication rates were similar in both groups, and treatment was considered equivalent.

Combined modality therapy of Hodgkin's disease: 10-year results of National Cancer Institute of Canada Clinical Trials Group multicenter clinical trial.

The purpose of this study was to compare four methods of treatment for stage III-IV Hodgkin's disease. Between January 1972 and September 1976, 266 patients with stage IIIB, IVA, and IVB Hodgkin's disease from 21 cancer treatment centers across Canada were registered as eligible; 40 were found to be ineligible. Of the 226 remaining patients, only seven were followed for less than 10 years. All patients received three courses of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, which induced a complete response (CR) in 36%; an additional 42% obtained adequate disease control. Patients were randomly assigned to (1) treatment with radiation to the abdomen and mantle (group AX3, 62 patients) or (2) continue their treatment with an additional three courses of MOPP (group A, 105 patients). For the A group, a second randomization took place 3 months later (regardless of status at that time) to (1) no further treatment (AC6, 23 patients), (2) radiotherapy to the abdomen and mantle (AX6, 48 patients), or (3) maintenance chemotherapy at 3-month intervals for 1 year (AC10, 26 patients). The survival of AX3 patients was somewhat better than for the A group, but the difference was not significant (P = .0565). However, there was a significant interaction (P = .0029) between age and treatment, so that among patients less than 30 years of age, the survival of the A group was better, whereas for older patients, treatment with AX3 resulted in improved survival. Age itself remained a significant prognostic factor for survival after controlling for the amount of radiotherapy delivered to the abdomen and the dose intensity of vincristine for the first three courses of chemotherapy. The addition of radiation therapy to MOPP significantly reduced the frequency of nodal relapses. These results suggest that combined modality therapy may be beneficial for some patients with Hodgkin's disease and that age must be carefully considered in interpreting the results of clinical trials in Hodgkin's disease.

The Screening Mammography Program of British Columbia: pilot study.

A government-funded pilot project of high volume screening mammography was conducted in Vancouver, British Columbia. 7,100 women were screened over a 9-month period, averaging 43 women per day at a cost of $33.81 per woman screened. 722 (10%) had abnormal mammograms; 144 received breast biopsies; and 29 were diagnosed with cancer. The overall cancer detection rate was 4.1 per 1,000 (0.8 and 4.8 for incident and prevalent cases, respectively). The staging distribution for the 29 cancer cases was 5, 15, 8 and 1 for in situ, stage I, II and III, respectively.

Early breast cancer: detection of recurrence after conservative surgery and radiation therapy.

To determine the clinical and mammographic features of recurrent breast cancer after tumorectomy and radiation therapy, the authors reviewed the clinical history and serial mammograms of 48 patients with suspected recurrence. Of patients with recurrent disease, seven had positive mammograms alone, nine had positive findings at physical examination alone, and eight had both positive mammograms and positive results of physical examination. Positive mammographic findings included the development of new fine calcifications (six patients), a new mass (five patients), mass and calcifications (one patient), increasing opacity (two patients), or skin thickening (one patient). Patients in whom the breast recurrence was detected mammographically alone were less likely to develop metastatic disease in subsequent follow-up than when results of physical examination were positive at the time of breast recurrence. Serial mammographic and clinical examinations are complementary for optimal detection of recurrence after conservative surgery and radiation therapy.

Postmastectomy lymphedema treated with the Wright linear pump.

Fifteen patients with postmastectomy lymphedema of the arm were treated with the Wright linear pump, a programmable, gradient pressure, sequential, intermittent compression pump. The group comprised volunteers in whom conservative measures had failed. This is a phase II trial to determine the efficacy of the pump. All patients had subjective improvement. Objectively, all showed a reduction in edema, but this was of variable degree and depended on the amount of pre-existing lymphedema in the arm. The Wright linear pump is easy to use and treatment was well tolerated. No fluid overload occurred due to treatment and no other medical problems were encountered. The Wright linear pump seems more effective than other pneumatic intermittent compression pumps available.

Breast cancer after treatment for osteosarcoma.

Two cases of patients with primary osteosarcoma who developed subsequent new primary infiltrating ductal carcinoma of breast are presented. The relationship of irradiation from diagnostic radiology, chemotherapy given, and possible genetic factors are discussed. A recommendation for the lifetime follow-up program of a patient with osteosarcoma should include careful attention to breast self-examination and regular breast examination by the attending physician.

Radiation dose and second breast cancer.

Amongst 14,000 women with breast cancer treated between 1946 and 1982, 194 developed a second primary tumour in the contralateral breast more than one year after diagnosis of the first primary. The radiation dose to the contralateral breast was calculated for each member of this group and also for members of a control group matched for age, year of diagnosis and survival time. Comparison of the groups provides no evidence for radiation induced carcinogenesis on the contralateral breast in these patients.

Bacille Calmette-Guérin as maintenance therapy for non-Hodgkin's lymphoma.

Following complete remission of non-Hodgkin's lymphoma by chemotherapy, irradiation or both, 44 patients were studied to assess the value of bacille Calmette-Guérin (BCG) as maintenance therapy. Patients with stage LI, EI or EII disease were allocated at random to receive BCG or no further maintenance therapy, and those with stage LII, LIII, EIII or IV disease received BCG therapy or orally administered cyclophosphamide. BCG had no effect on the duration of remission or the overall survival from the time of randomization. However, after the first recurrence there was a significant improvement in survival in the patients who had received BCG maintenance therapy.

Laparotomy for staging of Hodgkins' disease.

Laparotomy was used for staging Hodgkin's disease in a selected group of 71 patients over a 9-year period at the Cancer Control Agency of British Columbia. Operative results altered the staging in 30 patients and the treatment in 28 patients. Negative lymphangiograms were found to predict accurately the absence of abdominal lymph-node involvement. No investigation was as accurate as laparotomy in identifying subdiaphragmatic Hodgkin's disease. There were no operative deaths and the overall morbidity was 18%. The value of staging laparotomy depends on the adjustment of therapy to match the changes in staging made as a result of this procedure. Of specific advantage is the avoidance of unnecessary chemotherapy. Improved long-term survival as a result of staging laparotomy has yet to be proven.