 |
Other Guidelines
Guidelines on endocrine therapy of breast cancer
1. Ductal carcinoma in situ
-
Rationale
Two trials have been conducted assessing the value of adjuvant tamoxifen in
reducing breast relapse after breast conservation treatment in Ductal carcinoma in
situ (DCIS): the National Surgical Adjuvant Breast Project (NSABP) B-24
trial and the (UK DCIS) trial.
Published data are available from the B-24 trial
[1]
[2]. In this study, 1804 patients were randomly assigned to lumpectomy
plus radiation therapy (50 Gray) and placebo (n=902) or lumpectomy plus
radiotherapy and tamoxifen (20 mg daily for 5 years, n=902). Involved
margins after lumpectomy (16% in both groups) were allowed. After a median
follow-up of 74 months (57-93 months), women in the tamoxifen group had
significantly fewer breast cancer events (and particularly local recurrences)
at 5 years compared with those in the placebo group (8.2% versus 13%, P=0.009).
The authors stated that the combination of a lumpectomy, radiotherapy and
tamoxifen was effective in the prevention of invasive breast cancer in patients
with DCIS.
No width of margin clearance on histology was required in this trial and this
is likely to explain the high recurrence rate in both arms; the UK trial is
likely to give a similar result for the same reason. This trial has raised a
number of questions of interpretation.
a. The trial results are from a relatively short-term follow-up. In invasive
carcinomas, tamoxifen-resistance develops with time and it seems likely to do
so in DCIS.
b. Over 80% of patients had DCIS lesions less than 1 cm. Patients for this
study appear to have been selected in contributory centres for smaller lesions,
as in population-based series screen-detected DCIS are, on average, of larger
size. Despite over 805 of the patients having lesions smaller than 1 cm, the
incidence of invasive ipsilateral breast recurrences after 5 years was 9.3 and
6.1%, in the placebo and tamoxifen groups, respectively, which must be judged
unacceptably high rates. This has been ascribed to insufficient attention to
margin clearance.
c. The effect of tamoxifen is particularly seen in patients with known risk
factors for breast relapse: younger age (≤49 years), positive margins,
the presence of comedo necroses and tumours detected by clinical examination
(usually larger lesions). This raises the question of the magnitude of the
absolute effect of tamoxifen in patients with a low risk of relapse.
d. At a median of 4 years, the 902 patients treated with tamoxifen had 29 fewer
invasive breast cancers and 17 fewer in-situ carcinomas, but eight extra
thromboembolic events and five extra endometrial cancers
[3].
e. Tamoxifen must not be relied upon to compensate for inadequate local
treatment.
| Quality objective |
Outcome measure
|
|
In patients treated by wide local excision (WLE) and intact breast irradiation
(RT), to keep local (in-breast) recurrence to an acceptable minimum |
- In-breast relapse rates must be below 15% at 10 years.
- Routine prescription of tamoxifen following WLE is not recommended
(outside of clinical trials).
|
| Quality objective |
Outcome measure
|
|
To avoid over-treatment of those at low risk of recurrence (low grade and
smaller tumours with widely-clear histological margins)
|
Tamoxifen should not be added to WLE in those patients judged to be
at low risk of recurrence.
|
| Quality objective |
Outcome measure
|
|
To lower the recurrence rate where there is a high risk of local recurrence,
e.g. patient desires breast conserving surgery but clear margins cannot be
achieved.
|
- Tamoxifen may be prescribed for 5 years in patients with ER-positive
tumours.
- The patient must be told that the risk of recurrence is higher than that
achieved by mastectomy
- Explanation in terms of absolute risk-reduction over time must be given.
- The patient must be told that the only information available at present on
the use of hormonal therapy in DCIS relates to the reduction of risk in the
short term.
- The patient must be advised of the risk of serious adverse effects.
|
|
|