Purpose To assess the clinical significance of tumor-infiltrating FOXP3-positive regulatory T cells (TR) in breast cancer patients with long-term follow-up. Patients and Methods FOXP3-positive TR were detected by immunohistochemistry with our new, extensively characterized FOXP3 monoclonal antibody, 236A/E7. Numbers of FOXP3-positive lymphocytes in tissue microarray cores from pure ductal carcinoma in situ (DCIS; n = 62), invasive breast cancer (n = 237) or from comparable areas of normal terminal duct lobular breast tissue (n = 10) were determined. A median cutoff of ≥ 15 defined patients with high numbers of TR. Results TR numbers were significantly higher in in situ and invasive breast carcinomas than in normal breast; invasive tumors have significantly higher numbers than DCIS (P = .001). High numbers of FOXP3-positive TR identified patients with DCIS at increased risk of relapse (P = .04) and patients with invasive tumors with both shorter relapse-free (P = .004) and overall survival (P = .007). High...

Quantification of Regulatory T Cells Enables the Identification of High-Risk Breast Cancer Patients and Those at Risk of Late Relapse

PURPOSETo determine if the long-term increase of recurrence for breast cancer is stable or slowly decreasing, or if it ever reaches zero; and to determine the effect of prognostic factors on the hazard of recurrence.METHODSAll patients entered onto the seven completed and unblinded Eastern Cooperative Oncology Group (ECOG) coordinated studies of postoperative adjuvant therapy for breast cancer were analyzed in terms of annual hazard of recurrence of breast cancer.RESULTSFor the entire group, the peak hazard of recurrence occurred in the interval of 1 to 2 years. The hazard decreased consistently in the interval of 2 to 5 years. Beyond 5 years, the hazard of recurrence decreased very, very slowly through year 12. The average hazard of recurrence between years 5 and 12 for the entire population was 4.3% per year. The pattern of a peak hazard of recurrence during the first 5 years with a slowly decreasing hazard of recurrence beyond 5 years was also observed to varying degrees in most subsets. Higher risk su...

Annual hazard rates of recurrence for breast cancer after primary therapy.

We analyzed the relation between age at diagnosis and relative survival (ratio of observed to expected survival) in 57,068 women in Sweden in whom breast cancer was diagnosed in 1960 to 1978 (about 98 percent of all cases). Women who were 45 to 49 years old had the best prognosis, with a relative survival exceeding that of the youngest patients (less than 30 years) by 7.6 to 12.9 percent at different periods of observation. Relative survival declined markedly after the age of 49--particularly in women aged 50 to 59--and the oldest women (greater than 75) had the worst rate. The difference in relative survival between those older than 75 and those 45 to 49 increased from 8.6 percent at 2 years to 12.2, 20.3, and 27.5 percent after 5, 10, and 15 years of follow-up, respectively. The long-term annual mortality rate due to breast cancer approached 1 to 2 percent at the premenopausal ages but exceeded 5 percent throughout the period of observation in the oldest age group. An understanding of the biologic basis for the complex relation between age and prognosis might provide a better understanding of the natural history of breast cancer in women.

The relation between survival and age at diagnosis in breast cancer.

Objective: To assess the impact of the NHS breast screening programme on mortality from breast cancer in women aged 55-69 years over the period 1990-8. Design: Age cohort model with data for 1971-89 used to predict mortality for 1990-8 with assumption of no major effect from screening or improvements in treatment until after 1989. Effect of screening and other factors on mortality estimated by comparing three year moving averages of observed mortality with those predicted (by five year age groups from 50-54 to 75-79), the effect of screening being restricted to certain age groups. Setting: England and Wales. Subjects: Women aged 40 to 79 years. Results: Compared with predicted mortality in the absence of screening or other effects the total reduction in mortality from breast cancer in 1998 in women aged 55-69 was estimated as 21.3%. Direct effect of screening was estimated as 6.4% (range of estimates from 5.4-11.8%). Effect of all other factors (improved treatment with tamoxifen and chemotherapy, and earlier presentation outside the screening programme) was estimated as 14.9% (range 12.2-14.9%). Conclusions: By 1998 both screening and other factors, including improvements in treatment, had resulted in substantial reductions in mortality from breast cancer. Many deaths in the 1990s will be of women diagnosed in the 1980s and early 1990s, before invitation to screening. Further major effects from screening and treatment are expected, which together with cohort effects should result in further substantial reductions in mortality from breast cancer, particularly for women aged 55-69, over the next 10 years.

https://www.bmj.com/content/bmj/321/7262/665.full.pdf

Effect of NHS breast screening programme on mortality from breast cancer in England and Wales, 1990-8: comparison of observed with predicted mortality.

Objectives: To determine what proportion of oncology patients receiving conventional medical treatment also use complementary treatments; to assess which complementary treatments are the most popular and to assess patients9 motivation for using them; to evaluate associated advantages and risks. Design: Postal screening questionnaire followed by semistructured interview. Setting: Two hospitals in inner London. Subjects—600 unselected oncology patients aged 18 or over who had known their diagnosis of cancer for at least three months. Main outcome measures: Prevalence and demography of use of complementary therapies; patients9 motivation and expectations of complementary therapies; areas of satisfaction and dissatisfaction associated with conventional and complementary therapies. Results: 415 (69%) patients returned the questionnaire. 16% had used complementary therapies. The most popular were healing, relaxation, visualisation, diets, homoeopathy, vitamins, herbalism, and the Bristol approach. Patients using complementary therapies tended to be younger, of higher social class, and female. Three quarters used two or more therapies. Therapies were mostly used for anticipated antitumour effect. Ill effects of diets and herb treatments were described. Satisfaction with both conventional and complementary therapies was high, although diets often caused difficulties. Patients using complementary therapies were less satisfied with conventional treatments, largely because of side effects and lack of hope of cure. Benefits of complementary therapies were mainly psychological. Conclusions: A sizeable percentage of patients receiving conventional treatments for cancer also use complementary therapies. Patient satisfaction with complementary therapies, other than dietary therapies, was high even without the hoped for anticancer effect. Patients reported psychological benefits such as hope and optimism.

/pdf/pursuit-and-practice-of-complementary-therapies-by-cancer-ajn2978n37.pdf

Pursuit and practice of complementary therapies by cancer patients receiving conventional treatment

A retrospective analysis was made of 3878 cases of breast carcinoma first seen in Edinburgh from 1954 to 1964. During this time there was a policy to treat breast cancer by simple mastectomy and x-ray therapy, and over 90% of cases classified as international stages I and II were so treated. The mortality in these women was compared with that in an equivalent normal population using Scottish national age-specific death rates. For every year of follow-up within 20 years of initial treatment there was an excess mortality from all causes. There was an overall excess mortality of 58% among patients with breast cancer 15-20 years after initial treatment, and 20 times more deaths occurred in this period from breast cancer than in a normal population. For patients disease-free after 15 years there was still a 28% excess mortality from all causes. Factors known to be of major prognostic significance for five-year survivorship had less influence than might have been expected when the ratio of observed to expected deaths was considered for longer periods of follow-up. The effect of clinical staging (I, II, or III), though initially marked, largely disappeared by the 10th year of follow-up, and after allowing for age there was no evidence beyond 10 years of an effect on survival of the original stage of the disease. Similarly, the effect of tumour size on survival disappeared after 10 years. Women who were premenopausal at presentation still had a significant excess of deaths in the fourth quinquennium of follow-up. In the menopausal and postmenopausal groups combined there was still a small non-significant excess of deaths from all causes after 15 years but this almost disappeared when patients who had already relapsed were excluded. In terms of overall mortality only patients who have undergone the menopause before presentation and who are disease-free 15 years after primary treatment may prove to be cured by conventional techniques such as simple mastectomy and postoperative radiotherapy.

https://www.bmj.com/content/bmj/2/6200/1247.full.pdf

A O Langlands

Papers

Long-term survival of patients with breast cancer: a study of the curability of the disease.