Intended for healthcare professionals


Effect of hormone replacement therapy on the pathological stage of breast cancer: population based, cross sectional study

BMJ 2000; 320 doi: (Published 05 February 2000) Cite this as: BMJ 2000;320:348
  1. Sheila Stallard, staff grade surgeon (dr37d{at},
  2. Janet C Litherland, consultant radiologista,
  3. Carolyn M Cordiner, consultant radiologista,
  4. Hilary M Dobson, consultant radiologista,
  5. W David George, professor of surgerya,
  6. Elizabeth A Mallon, consultant pathologista,
  7. David Hole, principal epidemiologistb
  1. a University Departments of Surgery and Pathology, North Glasgow Hospitals University NHS Trust, Glasgow G11 6NT
  2. b West of Scotland Cancer Surveillance Unit, University Department of Public Health, Glasgow G12 8RZ
  1. Correspondence to: S Stallard
  • Accepted 16 August 1999

Hormone replacement therapy is being used increasingly. Although it is known that the risk of developing breast cancer is slightly increased with long term use,1 hormone replacement does not seem to adversely affect mortality from breast cancer.2

Studies have suggested that users of hormone replacement who get breast cancer develop tumours with “favourable” pathological features compared with non-users. One study included women who had been detected at screening and women who had presented with symptoms, with more screen detected women in the study group (users) than in the controls (non-users).2 Another study compared type of tumour in users and non-users in a screen detected population alone3 and showed that grade 1, node negative tumours were more common in the users.

Women with breast cancer who have used hormone replacement, however, may be more likely to have a cancer that was missed at screening; we have shown that women who develop such cancers (interval cancers) within a year of screening are twice as likely to have been using hormone replacement when they were screened.4 We compared pathological features of tumours in both screen detected and interval cancers to assess whether previous use of hormone replacement therapy improves prognosis among women who develop breast cancer.

Patients, methods, and results

The study population comprised all 1130 women aged 50-64 years who underwent routine breast screening during May 1988 to December 1993 in the area of Scotland covered by the West of Scotland Breast Screening Unit and who either had a screen detected cancer or developed an interval cancer. Data on interval cancers were collected up to the end of 1996. Current use of hormone replacement (yes/no) had been recorded by radiographers at the time of screening and also at assessment for women with screen detected cancers. The case notes of half the women with interval cancers were reviewed to check whether use of hormone replacement at the time of presentation was the same as at their last screening. Seventeen women were excluded because use of hormone replacement was unknown, leaving 1113 patients for analysis.

Of the 815 women with screen detected cancers, 100 (12.3%) were using hormone replacement when they were screened. Of the 298 women with interval cancer, 66 (22.1%) were using hormone replacement; use at diagnosis was the same as at their previous screen. Of the total number of women studied, therefore, 166 (14.9%) were using hormone replacement at the time they developed breast cancer.

We found no difference in type, size, or grade of tumour in users compared with non-users (table). Twenty four per cent of users developed well differentiated tumours (tubular, mucoid, and invasive ductal grade 1 cancers) compared with 22% of non-users. This equates to an odds ratio of 0.98 (95% confidence interval 0.63 to 1.50). Seventy seven per cent of users were node negative compared with 67% of non-users. There was no difference in mean tumour size (mean difference 0.25 mm (−2.02 mm to 2.53 mm)) in users compared with non-users. No difference was seen in the distribution of the Nottingham prognostic index5 between the two groups. Eight per cent of women using hormone replacement developed ductal carcinoma in situ compared with 15% of non-users. When screen detected cancers were analysed alone, no differences were found between the type, grade, size, or nodal status in users compared with non-users.

Pathological features of breast cancer by use of hormone replacement therapy. Values are numbers (percentages) unless stated otherwise

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Our results do not support the commonly held view that women using hormone replacement therapy develop tumours with favourable prognostic features. Little information currently exists about the relation between the development of ductal carcinoma in situ and use of hormone replacement. Our numbers are small, and further studies are needed. We show, however, that women using hormone replacement do not develop poorer prognosis tumours, and this is reassuring to doctors prescribing hormone replacement therapy.


JCL, CMC, and HMD also work at the West of Scotland Breast Screening Centre, Glasgow.

Contributors: SS, JCL, and CMC initiated the present study, designed the project, collected data, and contributed to writing the paper. DH also helped to develop the original idea and study design. He carried out the statistical analysis and did the cross checks with the cancer registry. He has been closely involved in the writing and revising of the final paper. EAM reported the pathology of all the cases and was responsible for the pathology quality assurance in the screening cases. HMD discussed core ideas, collected data, helped in the interpretation of data, and is responsible for the quality assurance of the screening programme. WDG allowed his patients to be studied, discussed ideas and the interpretation of findings, and encouraged the project. SS is the guarantor for the paper.


  • Funding None.

  • Competing interests None declared.


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