Breast cancer sugery: a century after Halsted

In the early years of this century prevailing currents of medical opinion led to the imposition of surgery even more aggressive than the radical mastectomy proposed by Halsted to treat breast cancer. More recently breast conservation surgery has become established but is always flanked by additional local treatment, and often by systemic therapy. Studies conducted in Milan were the first to demonstrate that conservative surgery plus an adjuvant therapy such as radiotherapy is efficacious in treating small-size breast cancer. As the year 2000 approaches it has become clear that breast cancer is curable in a high proportion of cases and attention is turning to improving the aesthetic outcome of the surgery, and to investigating the biological and genetic factors that influence the disease.Work presented at the 60th Anniversary Symposium of the Cancer Institute and Cancer Institute, Hospital, Tokya, held at September 1994     

Breast cancer

Breast cancer remains a public-health issue on a global scale. We report new information about the disease from the past 5 years. Early age at first birth, increasing parity, and tamoxifen use are related to long-term lifetime reduction in breast-cancer risk. Ductal carcinomas in situ has been suggested to be renamed ductal intraepithelial neoplasia to emphasise its non-life-threatening nature. An alternative approach, the progenitor/stem cell theory, predicts that only some tumour cells cause cancer progression and that these should be targeted by treatment. Mammography and ultrasonography are still the most effective for women with non-dense and dense breast tissues, respectively. Additionally, MRI, lymphatic mapping, the nipple-sparing mastectomy, partial breast irradiation, neoadjuvant systemic therapy, and adjuvant treatments are promising for subgroups of breast-cancer patients. Although tamoxifen can be offered for endocrine-responsive disease, aromatase inhibitors are increasingly used. Assessment of potential molecular targets is now important in primary diagnosis. Tyrosine-kinase inhibitors and other drugs with anti-angiogenesis properties are currently undergoing preclinical investigations.     

Thyroid carcinomas after irradiation for a first cancer during childhood

BACKGROUND: The thyroid gland is among the most radiosensitive organs. However, little is known about the long-term risk of developing a thyroid tumor after fractionated external radiotherapy for cancer during childhood. OBJECTIVE: To study the long-term risk of developing a thyroid tumor in 4096 three-year survivors of childhood cancer treated between May 1942 and December 1985 in 8 centers in France and the United Kingdom, 2827 of whom had received external radiotherapy. METHODS: A wide range of radiation doses were given to the thyroid: 1164 children received less than 0.5 Gy and 812 received more than 5.0 Gy, the average dose being 7.0 Gy. RESULTS: After mean follow-up of 15 years (range, 3-45 years), 14 patients-all of whom had received radiotherapy-developed a clinical thyroid carcinoma. Within the cohort, the relation between radiation dose to the thyroid and risk of thyroid carcinoma and adenoma was similar to that observed in patients who received radiotherapy during childhood for other reasons, such as an excess relative risk per gray of 4 to 8, up to a few gray. In contrast, compared with thyroid cancer incidence in the general population, the standardized incidence of thyroid carcinoma was much higher than expected from the dose-response relationship estimated within the cohort and from patients who received radiotherapy during childhood for other reasons: a dose of 0.5 Gy was associated with a standardized incidence ratio of 35 (90% confidence interval, 10-87) and a dose of 3.6 Gy with a standardized incidence ratio of 73 (90% confidence interval, 28-153). We did not show a reduction in excess relative risk per gray with use of an increasing number of fractions. CONCLUSION: Although we cannot estimate the exact proportion, it is probable that some or all children who are treated for cancer are predisposed to developing a thyroid carcinoma.     

Pulmonary arterial hypertension after childhood cancer therapy and bone marrow transplantation

According to the Third World Symposium on Pulmonary Arterial Hypertension (PAH), chemotherapy is considered to be one of the possible risk factors for patients developing PAH. However, to date, no literature has sufficiently addressed the risk, natural history, and effective treatment of this condition. We report our experience on how early diagnosis, detailed monitoring of disease course, and appropriate treatment application have led to a successful outcome of PAH management in childhood after cancer therapy. Our report reaffirmed the fact that PAH is now a recognized complication of chemotherapy and bone marrow transplantation for leukemia. Combined pulmonary vasodilator treatment has a beneficial effect in improving the patient's condition and functional status as suggested by initial acute pulmonary vasodilator testing.     

Breast cancer screening

The recommendations of the U.S. Preventive Services Task Force are reviewed in regard to screening for breast cancer. In contradistinction to those issued by some other national organizations, screening for breast cancer using mammography at ages 40–49 is not recommended. It is concluded that the scientific evidence is insufficient at present to recommend mammography screening for women aged 40–49. The recommendations of the task force are: all women over age 40 should receive an annual breast examination; all women should bave mammography every one or two years beginning at age 50 and concluding at approximately age 75 unless disease bas been detected; and it may be prudent to begin mammography at an earlier age for women at high risk of breast cancer. These recommendations are appropriate in light of the available evidence; though at present there is no evidence that clinical examination of the breasts at any age reduces breast cancer mortality; the upper age beyond which breast cancer screening no longer bas a significant effect in reducing breast cancer mortality is unknown; and there is no evidence that women at high risk for breast cancer benefit to a different degree from screening than women not at high risk.     

Risk factors for thyroid abnormalities after neck irradiation for childhood cancer

Thyroid evaluations were performed in 95 patients who received radiotherapy to the neck region for childhood cancer five to 34 years earlier. Fifty-six patients (61 percent) had at least one abnormality of serum free thyroxine index, serum thyroid-stimulating hormone (thyrotropin), or thyroid palpation. Seven had subnormal free thyroxine index and 40 had elevated thyrotropin concentrations. Thyroidal radiation doses of 3,000 or more rads and lymphangiography independently increased the risk (p ≤ 0.01) of an elevated serum thyrotropin concentration (present in 11 percent of patients with neither risk factor, 50 percent of those who underwent lymphangiography and received less than 3,000 rads, 46 percent of those who had 3,000 or more rads and no lymphangiography, and 76 percent of those with both), but duration of follow-up did not. Twenty-six patients had thyroid nodules and six others had diffuse thyroid enlargement. The frequency of palpable abnormalities increased with the follow-up time after radiation (30 percent of patients followed up less than 10 years had abnormalities versus 43 percent of those followed up 10 or more years, p = 0.03), but was not related to the serum thyrotropin level, radiation dose, or lymphanglography. Among 10 patients who had surgery for nodules, three had localized papillary thyroid carcinomas.     

Breast cancer in pregnancy

Breast cancer staging and treatment are possible during pregnancy, and should be defined in a multidisciplinary setting. Tumour biology, tumour stage, and gestational stage at diagnosis determine the appropriate approach. Surgery for breast cancer is possible during all trimesters of pregnancy. Radiotherapy is possible during pregnancy but, dependent on the fetal dose received, can result in poor fetal outcomes. The decision to give radiotherapy should be made on an individual basis. Evidence increasingly supports administration of chemotherapy from 14 weeks' gestation onwards. New breast cancer treatments might be applicable to pregnant patients, but tamoxifen and trastuzumab are contraindicated during pregnancy. Cancer treatment during pregnancy will decrease the need for early delivery and thus prematurity, which is a major concern in management of breast cancer in pregnancy.     

Thyroid cancer in childhood

The incidence, clinical presentation, and types of thyroid cancers presenting in childhood are reviewed. The role of antecedent radiation in papillary and follicular thyroid cancers and genetics of medullary thyroid carcinoma are discussed. Unique aspects of therapy and prognosis for the pediatric patient with thyroid carcinoma are addressed as well as a diagnostic approach to the child who presents with a neck mass.