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 situcompared 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.
Comment
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 situand 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.
Table.
Pathological features of breast cancer by use of hormone replacement therapy. Values are numbers (percentages) unless stated otherwise
| All cancers (n=1113)
|
Screen detected cancers (n=815)
|
||||
|---|---|---|---|---|---|
| Users (n=166) | Non-users (n=947) | Users (n=100) | Non-users (n=715) | ||
| Type and grade | |||||
| Ductal carcinoma in situ | 12 (7.9) | 133 (14.9) | 12 (12.5) | 128 (18.3) | |
| Invasive ductal cancer: | |||||
| Grade 1* | 36 (23.7) | 198 (22.2) | 23 (23.9) | 175 (25.1) | |
| Grade 2 | 52 (34.2) | 252 (28.3) | 34 (35.4) | 201 (28.8) | |
| Grade 3 | 19 (12.5) | 105 (11.8) | 7 (7.3) | 48 (6.9) | |
| Grade not known | 22 (14.5) | 133 (14.9) | 14 (14.6) | 98 (14.0) | |
| Lobular | 11 (7.2) | 59 (6.6) | 6 (6.3) | 39 (5.6) | |
| Other | 0 | 11 (1.2) | 0 | 9 (1.3) | |
| Missing data | 14 | 56 | 4 | 17 | |
| Significance | χ2=8.33, df=6, P=0.21 | χ2=4.26, df=6, P=0.64 | |||
| Size (mm)† | |||||
| <10 | 30 (23.4) | 186 (25.3) | 24 (31.6) | 171 (31.0) | |
| 10-19 | 51 (39.8) | 299 (40.7) | 35 (46.1) | 234 (42.4) | |
| 20-29 | 31 (24.2) | 140 (19.1) | 13 (17.1) | 96 (17.4) | |
| 30-39 | 8 (6.3) | 58 (7.9) | 2 (2.6) | 31 (5.6) | |
| 40-49 | 5 (3.9) | 30 (4.1) | 1 (1.3) | 11 (2.0) | |
| ⩾50 | 3 (2.3) | 21 (2.8) | 1 (1.3) | 9 (1.6) | |
| Missing data | 12 | 24 | 8 | 18 | |
| Significance | χ2=0.01, df trend=1, P=0.92 | χ2=0.63, df trend=1, P=0.43 | |||
| No of nodes† | |||||
| None | 96 (77.4) | 437 (66.7) | 58 (84.1) | 354 (73.8) | |
| <4 | 20 (16.1) | 150 (22.9) | 8 (11.6) | 95 (19.8) | |
| ⩾4 | 8 (6.5) | 68 (10.4) | 3 (4.3) | 31 (6.5) | |
| Missing data | 16 | 103 | 15 | 90 | |
| Significance | χ2=5.09, df trend=1, P=0.03 | χ2=2.74, df trend=1, P=0.1 | |||
| Nottingham prognostic index‡ | |||||
| Low | 65 (62.5) | 307 (57.5) | 44 (74.6) | 264 (67.2) | |
| Medium | 29 (27.9) | 180 (33.7) | 13 (22.0) | 109 (27.7) | |
| High | 10 (9.6) | 47 (8.8) | 2 (3.4) | 20 (5.1) | |
| Significance | χ2=1.34, P=0.51 | χ2=1.33, P=0.51 | |||
| Insufficient information | 50 | 280 | 29 | 194 | |
Includes tubular and mucoid tumours.
Excludes ductal carcinoma in situ and missing grades.
Nottingham prognostic index (in which a low score indicates a better prognosis than a high score) does not apply to cases of ductal carcinoma in situ.
Acknowledgments
JCL, CMC, and HMD also work at the West of Scotland Breast Screening Centre, Glasgow.
Footnotes
Funding: None.
Competing interests: None declared.
References
- 1.Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalyses of data from 51 epidemiological studies of 52 705 women with breast cancer and 108 411 without breast cancer. Lancet. 1997;350:1047–1059. [PubMed] [Google Scholar]
- 2.Gambrell RD. Update on hormone replacement therapy. Am Fam Physician. 1992;46:87–96S. [PubMed] [Google Scholar]
- 3.Harding C, Knox WF, Faragher EB, Baildam A, Bundred NJ. Hormone replacement therapy and tumour grade in breast cancer: prospective study in screening unit. BMJ. 1996;312:1646–1647. doi: 10.1136/bmj.312.7047.1646. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Litherland JC, Stallard S, Hole D, Cordiner C. The effect of hormone replacement therapy on the sensitivity of screening mammograms. Clinical Radiology. 1999;54:285–288. doi: 10.1016/s0009-9260(99)90555-x. [DOI] [PubMed] [Google Scholar]
- 5.Galea MH, Blamey RW, Elston CE, Ellis IO. The Nottingham prognostic index in primary breast cancer. Breast Cancer Research and Treatment. 1992;22:207–219. doi: 10.1007/BF01840834. [DOI] [PubMed] [Google Scholar]