Brtish Journal ot Cancer (1995) 7L 1142-1144
@) 1995 Stockton Press AJI nghts reserved 0007-0920/95 $12.00
EDITORIL
Adjuvant therapy for operable breast cancer; more answers, new questions
TJ Perren
ICRF Cancer Medicine Research Unit, St. James's University Hospital, Leeds, UK. On behalf of the ABC Trial Steering
Committee*
The first overview of systemic adjuvant treatment for early monal manipulation in women aged less than 50 with breast
breast cancer by The Early Breast Cancer Triallists' Col- cancer. Data from trials of adjuvant tamoxifen suggested a
laborative Group (EBCTCG) was published in 1990. It dem- significant reduction in the annual odds of recurrence, but no
onstrated. over a 5 year period, a significant improvement in significant reduction in mortality. Data with respect to
mortality for women over the age of 50 when treated with ovarian ablation were incomplete.
tamoxifen and for women under the age of 50 when treated The 1992 overview has unexpectedly shown that ovarian
with chemotherapy. ablation used as adjuvant therapy in this group of women
The publication in 1992 of the second EBCTCG overview results in a 30% (SD9) reduction in the annual odds of
provides us with reliable data over 10 years of follow-up recurrence and a 28% (SD9) reduction in the annual odds of
(Early Breast Cancer TInallists' Collaborative Group, death. The magnitude of this effect shows no sign of
1992a,b). It has answered a number of important questions, diminishing even after 15 years of follow-up.
provided some unexpected results and raised a series of new More detailed analyses of the tamoxifen trials in women
issues to be addressed by future research, particularly in aged less than 50 in the 1992 overview have also provided
terms of the potential benefits to be realised by combinations some surprises with respect to duration of tamoxifen
of systemic chemotherapy and hormonal therapies in women administration. The previous interpretation of these analyses
of all ages. was misleading. since patients treated with both tamoxifen
The 1992 overview has confirmed the efficacy of and chemotherapy had a shorter duration of tamoxifen
chemotherapy for women under the age of 50, and of tamox- administration (mean 1.6 years) than those treated with
ifen for women over the age of 50. For women aged less than tamoxifen alone (mean 2.6 years). Thus. comparisons of
50. the use of adjuvant combination chemotherapy reduces tamoxifen duration between trials were likely to have been
the annual odds of recurrence by 37% with a standard confounded by the use of chemotherapy. In the 1992 over-
deviation of ± 5% (SD5) and the annual odds of death by view. unconfounded analyses of tamoxifen duration in 2216
27% (SD6). For women over the age of 50, the use of women treated for a mean of 2.6 years have shown a reduc-
adjuvant tamoxifen reduces the annual odds of recurrence by tion in the annual odds of recurrence of 277% (SD7) and in
30% (SD2) and the annual odds of death by 19% (SD3). the annual odds of death of 17% (SDIO). not dissimilar to
Since the vast majority of women who develop recurrent the results achieved for women over the age of 50. Indeed.
breast cancer ultimately die from the disease, it is anticipated further breakdown of these data reveal that. when women
that. after sufficiently long periods of follow-up, the reduc- aged less than 50 are treated with tamoxifen for 2 years or
tion seen in the annual odds of death will match that seen for more, the reduction in the annual odds of recurrence is 43%
recurrence. To convert these figures into numbers which are (SD 1), and in the annual odds of death is 27%
more easily understood. a reduction in the annual odds of (SD17) - very similar to those figures described earlier for
death of about 30% equates to approximately 12 extra chemotherapy in this age group. However, it should be noted
women alive at 10 years for every 100 women treated with that because of relatively small numbers in these analyses the
stage II breast cancer, and approximately six extra women confidence intervals are much wider than those in the
alive at 10 years for every 100 women treated with stage I chemotherapy analyses. implying a degree of statistical ins-
breast cancer. Although these improvements do not appear tability to the results.
large, they should be considered in the context of the millions The first overview also suggested a limited role for
of women treated worldwide each decade for operable breast chemotherapy when given alone to women over the age of
cancer. Adjuvant treatment of just one million women could 50. for whom a significant reduction in the annual odds of
well prevent, or substantially delay, an additional 100 000 recurrence was demonstrated, but this did not translate into
deaths. a significant effect on mortality. The 1992 overview, however.
The first overview (Early Breast Cancer Triallists' Col- clearly shows that chemotherapy does in fact have a
laborative Group, 1990) suggested a limited role for hor- sigificant effect in this age group. reducing the annual odds
of recurrence by 22% (SD4). and the annual odds of death
by 14% (SD5).
Correspondence: TJ Perren Thus, for women aged less than 50. there are three effective
*P Barrett-Lee. Velindre Hospital. Cardiff; JM Bliss. Institute of treatments. namely chemotherapy. ovarian ablation and
Cancer Research. Sutton; J Brown. Brunel University. Uxbridge. tamoxifen. And for women over the age of 50 there are two
Middlesex; AM Brunt. North Staffordshire Royal Infirmary. Stoke; effective treatments, namely tamoxifen and chemotherapy.
A Cull. Western General Hospital. Edinburgh; S Denton. St Bar- What is not known with any accuracy at the present time is
tholomew's Hospital. London; H Earl. CRC Trials Umlt. Birmin- what happens when these treatments are combined and
gham. WD George. Western Infirmary. Glasgow: A Gould. Scottish whether the benefits are additive. Data now available from
Cancer Therapy Network. Edinburgh; A Harnett. Beatson Oncology the 1992 overview. shown in Table I. suggest that, for women
Centre. Glasgow; M Mason. Velindre Hospital. Cardiff; J Mossman.
UKCCCR. London; M Richards. Guy's Hospital. London; J Yar- aged less than 50. tamoxifen may be less effective when given
nold. Royal Marsden Hospital. Sutton; R Collins (Observer) ICRF in combination with chemotherapy. in that the additional
Clinical Tnrals Unit. Oxford. reductions in the annual odds of recurrence and death from
Received 15 June 1994; revised 15 February 1995; accepted 15 Feb- the addition of tamoxifen were only 7% (SD4) and 3%
ruary 1995 (SD5) respectively when compared with chemotherapy alone
@) 1995 Stockton Press AJI nghts reserved 0007-0920/95 $12.00
EDITORIL
Adjuvant therapy for operable breast cancer; more answers, new questions
TJ Perren
ICRF Cancer Medicine Research Unit, St. James's University Hospital, Leeds, UK. On behalf of the ABC Trial Steering
Committee*
The first overview of systemic adjuvant treatment for early monal manipulation in women aged less than 50 with breast
breast cancer by The Early Breast Cancer Triallists' Col- cancer. Data from trials of adjuvant tamoxifen suggested a
laborative Group (EBCTCG) was published in 1990. It dem- significant reduction in the annual odds of recurrence, but no
onstrated. over a 5 year period, a significant improvement in significant reduction in mortality. Data with respect to
mortality for women over the age of 50 when treated with ovarian ablation were incomplete.
tamoxifen and for women under the age of 50 when treated The 1992 overview has unexpectedly shown that ovarian
with chemotherapy. ablation used as adjuvant therapy in this group of women
The publication in 1992 of the second EBCTCG overview results in a 30% (SD9) reduction in the annual odds of
provides us with reliable data over 10 years of follow-up recurrence and a 28% (SD9) reduction in the annual odds of
(Early Breast Cancer TInallists' Collaborative Group, death. The magnitude of this effect shows no sign of
1992a,b). It has answered a number of important questions, diminishing even after 15 years of follow-up.
provided some unexpected results and raised a series of new More detailed analyses of the tamoxifen trials in women
issues to be addressed by future research, particularly in aged less than 50 in the 1992 overview have also provided
terms of the potential benefits to be realised by combinations some surprises with respect to duration of tamoxifen
of systemic chemotherapy and hormonal therapies in women administration. The previous interpretation of these analyses
of all ages. was misleading. since patients treated with both tamoxifen
The 1992 overview has confirmed the efficacy of and chemotherapy had a shorter duration of tamoxifen
chemotherapy for women under the age of 50, and of tamox- administration (mean 1.6 years) than those treated with
ifen for women over the age of 50. For women aged less than tamoxifen alone (mean 2.6 years). Thus. comparisons of
50. the use of adjuvant combination chemotherapy reduces tamoxifen duration between trials were likely to have been
the annual odds of recurrence by 37% with a standard confounded by the use of chemotherapy. In the 1992 over-
deviation of ± 5% (SD5) and the annual odds of death by view. unconfounded analyses of tamoxifen duration in 2216
27% (SD6). For women over the age of 50, the use of women treated for a mean of 2.6 years have shown a reduc-
adjuvant tamoxifen reduces the annual odds of recurrence by tion in the annual odds of recurrence of 277% (SD7) and in
30% (SD2) and the annual odds of death by 19% (SD3). the annual odds of death of 17% (SDIO). not dissimilar to
Since the vast majority of women who develop recurrent the results achieved for women over the age of 50. Indeed.
breast cancer ultimately die from the disease, it is anticipated further breakdown of these data reveal that. when women
that. after sufficiently long periods of follow-up, the reduc- aged less than 50 are treated with tamoxifen for 2 years or
tion seen in the annual odds of death will match that seen for more, the reduction in the annual odds of recurrence is 43%
recurrence. To convert these figures into numbers which are (SD 1), and in the annual odds of death is 27%
more easily understood. a reduction in the annual odds of (SD17) - very similar to those figures described earlier for
death of about 30% equates to approximately 12 extra chemotherapy in this age group. However, it should be noted
women alive at 10 years for every 100 women treated with that because of relatively small numbers in these analyses the
stage II breast cancer, and approximately six extra women confidence intervals are much wider than those in the
alive at 10 years for every 100 women treated with stage I chemotherapy analyses. implying a degree of statistical ins-
breast cancer. Although these improvements do not appear tability to the results.
large, they should be considered in the context of the millions The first overview also suggested a limited role for
of women treated worldwide each decade for operable breast chemotherapy when given alone to women over the age of
cancer. Adjuvant treatment of just one million women could 50. for whom a significant reduction in the annual odds of
well prevent, or substantially delay, an additional 100 000 recurrence was demonstrated, but this did not translate into
deaths. a significant effect on mortality. The 1992 overview, however.
The first overview (Early Breast Cancer Triallists' Col- clearly shows that chemotherapy does in fact have a
laborative Group, 1990) suggested a limited role for hor- sigificant effect in this age group. reducing the annual odds
of recurrence by 22% (SD4). and the annual odds of death
by 14% (SD5).
Correspondence: TJ Perren Thus, for women aged less than 50. there are three effective
*P Barrett-Lee. Velindre Hospital. Cardiff; JM Bliss. Institute of treatments. namely chemotherapy. ovarian ablation and
Cancer Research. Sutton; J Brown. Brunel University. Uxbridge. tamoxifen. And for women over the age of 50 there are two
Middlesex; AM Brunt. North Staffordshire Royal Infirmary. Stoke; effective treatments, namely tamoxifen and chemotherapy.
A Cull. Western General Hospital. Edinburgh; S Denton. St Bar- What is not known with any accuracy at the present time is
tholomew's Hospital. London; H Earl. CRC Trials Umlt. Birmin- what happens when these treatments are combined and
gham. WD George. Western Infirmary. Glasgow: A Gould. Scottish whether the benefits are additive. Data now available from
Cancer Therapy Network. Edinburgh; A Harnett. Beatson Oncology the 1992 overview. shown in Table I. suggest that, for women
Centre. Glasgow; M Mason. Velindre Hospital. Cardiff; J Mossman.
UKCCCR. London; M Richards. Guy's Hospital. London; J Yar- aged less than 50. tamoxifen may be less effective when given
nold. Royal Marsden Hospital. Sutton; R Collins (Observer) ICRF in combination with chemotherapy. in that the additional
Clinical Tnrals Unit. Oxford. reductions in the annual odds of recurrence and death from
Received 15 June 1994; revised 15 February 1995; accepted 15 Feb- the addition of tamoxifen were only 7% (SD4) and 3%
ruary 1995 (SD5) respectively when compared with chemotherapy alone
