FYI
Veronesi U, Maisonneuve P, Costa A, Sacchini V, Maltoni C, Robertson C,
Rotmensz N, and Boyle P., "Prevention of breast cancer with
tamoxifen:
preliminary findings from the Italian randomised trial among
hysterectomised women. Italian Tamoxifen Prevention Study", The Lancet,
July 11, 1998, Vol. 352, Num. 0, pp. 93-97
"Background: Tamoxifen is a candidate chemopreventive agent in breast
cancer, although the drug may be associated with the development of
endometrial cancer. Therefore we did a trial in hysterectomised women
of tamoxifen as a chemopreventive."
"Methods: In October, 1992, we started a double-blind
placebo-controlled, randomised trial of tamoxifen in women (mainly in
Italy) who did not have breast cancer and who had had a hysterectomy.
Women were randomised to receive tamoxifen 20 mg per day or placebo,
both orally for 5 years. The original plan was to follow the
intervention phase by 5 years' follow-up. In June, 1997, the trialists
and the data-monitoring committee decided to end recruitment primarily
because of the number of women dropping out of the study. Recruitment
ended on July 11, 1997, and the study will continue as planned. The
primary endpoints are the occurrence of and deaths from breast cancer.
This preliminary interim analysis is based on intention-to-treat."
"Findings: 5408 women were randomised; participating women have a
median follow-up of 46 months for major endpoints. 41 cases of breast
cancer occurred so far; there have been no deaths from breast cancer.
There is no difference in breast-cancer frequency between the placebo
(22 cases) and tamoxifen (19) arms. There is a statistically
significant reduction of breast cancer among women receiving tamoxifen
who also used hormone-replacement therapy during the trial: among 390
women on such therapy and allocated to placebo, we found eight cases of
breast cancer compared with one case among 362 women allocated to
tamoxifen. Compared with the placebo group, there was a significantly
increased risk of vascular events and hypertriglyceridaemia among women
on tamoxifen."
"Interpretation: Although this preliminary analysis has low power, in
this cohort of women at low-to-normal risk of breast cancer, the
postulated protective effects of tamoxifen are not yet apparent. Women
using hormone-replacement therapy appear to have benefited from use of
tamoxifen. There were no deaths from breast cancer recorded in women in
the study. It is essential to continue follow-up to quantify the
long-term risks and benefits of tamoxifen therapy"
"However, side-effects of Tamoxifen include an increased occurrence
of endometrial cancer."
"In June, 1997, the trialists and the data-monitoring committee
decided to end recruitment because of the number of women dropping out
of the study and the side-effect profile of tamoxifen."
"The decision to recruit only hysterctomised women was based on the
consideration that tamoxifen could produce an additional risk of
endometrial cancer."
"56 women experienced 64 events of thrombophlebitis,
phelbothrombosis, or embolus (or a combination) during the course of
this study: 18 women on placebo and 38 on tamoxifen (p=0..0053). 42
events were superficial phlebitis, with nine women having a diagnosis
of deep-vein thrombosis, six on tamoxifen and three on placebo."
"There were 14 documented cerebrovascular ischaemic events: five on
placebo and nine on tamoxifen (p=0.27). All five confirmed strokes
occurred in the tamoxifen arm. Based on the incidence of stroke in
Italy, it was estimated that the number of strokes seen in this study
was less than to be expected in a group of women this age. (After the
"freezing" of the data set, there was a further stroke and one
transient ischaemic attack, both in women on placebo)."
"Hypertriglyceridaemia was not looked for specifically at each
follow-up visit, and the study relies on self-reports from patients and
physicians and subsequent confirmation from laboratory findings. 17
women in the study had hypertriglyceridaemia: two on placebo and 15 on
tamoxifen (p=0.0013). This information almost certainly underestimates
the occurrence of hypertriglyceridaemia in women in the study."
"The principal investigators were concerned about the large numbers
of women withdrawing from the study, the unexpected finding with
hypertriglyceridaemia, the findings about vascular events, and the
number of well women complaining about the side-effects of
tamoxifen."
"The excess of hypertriglyceridaemia seen in women receiving
tamoxifen in our study appears to be occurring among women in whom a
diagnosis of hypertriglyceridaemia has not previously been made.
Although this is still a rare event, and it may be being underestimated
by the lack of direct focused question and examination in the follow-up
visits, the relative risk is large."
"The NSABP-14 trial showed a significant advantage to women who
received tamoxifen for 5 years in the adjuvant setting. Women on
tamoxifen were then radomised to either further 5 years of tamoxifen or
placebo. Through 4 years after the reassignment of tamoxifen-treated
patients to continued therapy or placebo, advantages in disease-free
survival (92 vs 86%, p=0.003) and distant-disease-free survival (96 vs
90%, p=0.01) were found for those who discontinued tamoxifen. Survival
was 96% for those who discontinued the drug compared with 94% for those
who continued the drug (p=0.08). These data could be interpreted as
being compatible with the hypothesis that long-term tamoxifen therapy
is associated with a more aggressive form of breast-cancer recurrence.
It is essential to monitor the mortality rate from breast cancer among
women receiving tamoxifen prophylactically. Otherwise there is a risk
that well women may be prescribed tamoxifen when experience of
long-term effects is lacking in such a population."
"In conclusion, tamoxifen was not significantly protective against
breast cancer in women at normal or slightly reduced risk of the
disease, at least in the duration of our follow-up. Women using
hormone-replacement therapy benefited from tamoxifen administration:
these preliminary findings require further investigation of the impact
of antioestrogens on users of such therapy. Whether the action is
limited to women receiving hormone-replacement therapy transdermally or
is present also in women using oral treatment should also be
investigated. It is notable that no deaths from breast cancer have yet
been observed in the entire cohort and a much longer follow-up will be
needed to quantify the impact of tamoxifen use on breast-cancer
mortality and other long-term risks and benefits of tamoxifen
therapy."
molly53 wrote:
> Hello everyone. I am new to this group having been diagnosed with bc
> in 2003. I have been on tamoxifen 3 years now and experiencing
> numbness, tingling and all sorts of strange twitchy feelings in my
> legs, sort of like what I imagine diabetic neuropathy feels like. My dr
> thinks its from the tamoxifen, but it doesn't seem to be a very common
> side effect. Has anyone else experienced this? And what the heck do you
> do about it? 
tamoxifen side effect? 
Linear Mode
