The recommendations derived from the existing clinical trials of
postmastectomy adjuvant radiation therapy seem to parallel the
lessons learned from the trials of postoperative adjuvant
chemotherapy conducted during the previous 20 to 30 years. From the
various meta-analyses of adjuvant chemotherapy trials, we have
learned that patient subgroupswhen arranged from negative lymph
nodes to positive nodes to increasing number of positive
nodesall have nearly the same proportion of reduction in risk
of recurrence. However, the absolute difference in risk of recurrence
is much greater in the subgroup of patients with multiple positive
lymph nodes. These principles probably hold true for postmastectomy
radiation therapy as well.
This paper by Marks and colleagues is very good, although it seems to
overstate the populations who may benefit from postmastectomy
radiation. The formidable task in the next several years is to
identify patients with an increased odds of local recurrence,
notwithstanding the current systemic therapy and modern surgical
techniques used in this country. These will be women for whom the
addition of radiation therapy would result in significant
improvements in local control and, hopefully, survival rates. It
would then be worth adding 6 weeks of radiotherapy to the breast
cancer treatment regimen, which can already consist of modified
radical mastectomy, with or without immediate reconstruction, several
months of intravenous chemotherapy, and then 5 years of tamoxifen
(Nolvadex). The concept of absolute reduction in risk is important to
discuss thoroughly with the patient since the complications of
radiation therapy can be more severe and disabling than the
complications of adjuvant chemotherapy.
Does Postmastectomy Radiation Improve Local Control and Survival?
The authors statistical presentation is excellent. Their
conclusion that postmastectomy radiation improves local control and
survival is new, however.
At the San Antonio Breast Cancer Symposium in 1998, Dr. Timothy
Whelan of Hamilton, Ontario, presented a meta-analysis of 18 studies
initiated between 1974 and 1982. The trials met the specific criteria
of randomization after mastectomy and axillary lymph node dissection,
use of the same adjuvant therapy in both arms (although sequencing of
radiation and chemotherapy varied), and median follow-up of at least
5 years. When the two large Danish trials[1,2] were removed from
statistical consideration, the odds ratio for recurrence and
mortality was 0.89, which was not statistically significant. With the
inclusion of the Danish trials, the meta-analysis supported the
concept that local radiation therapy significantly reduces the risk
of recurrence and death.
The Danish trials[1,2] and the recent British Columbia trial were
somewhat unusual. The relatively high rates of local recurrence in
the control arms of these trials had not been anticipated but might
be explained by the extent of axillary surgery. The median number of
axillary lymph nodes excised was 7 in the Danish trial and 11 in the
British Colombia trial. I disagree with the comment by Marks et al
that the median number of lymph nodes removed in the United States is
similar to that reported in these trials. That number may be correct
if the lymph nodes appear to be negative intraoperatively, but when
positive lymph nodes are recognized intraoperatively by the surgeon,
the median number of lymph nodes retrieved should be considerably
greater than 11.
Surgical technique plays a critical, but hard to quantify, role in
determining the risk of local failure. For example, the recent report
on the Danish trial showed that the local failure rate was 40% for
the 133 patients in whom only 0 to 3 lymph nodes were recovered, as
compared with 32% for the 511 patients in whom 5 to 9 lymph nodes
were removed, and 27% for the 211 patients in whom 10 lymph nodes
The Eastern Cooperative Oncology Group (ECOG) trial, which
followed more than 2,000 patients for over 12 years, showed a similar
trend related to a decreased number of lymph nodes examined and local
recurrence. In this study, 79% of women had 11 or more lymph nodes
excised. Overall, the study noted a much lower local recurrence rate
without the use of radiation therapy than was observed in the
Risk of Lymphedema and Reconstruction Difficulties
The authors touch only lightly on the risk of lymphedema. There was
three times the incidence of symptomatic lymphedema due to chest wall
radiation in the British Colombia trial (9% vs 3%), probably because
of scatter at the level of the larger lymphatic channels in the
axilla When an axillary field is added to an axillary dissection,
a majority of women will develop lymphedema, and to an extreme
degree. In the title of the present paper, an axillary field is
implied in the term locoregional radiotherapy.
There is also the issue of reconstruction after mastectomy, either
immediate or delayed, which this article avoids. Permanent changes
caused by radiation usually preclude certain kinds of simple
reconstructions, such as implants. Only relatively young, healthy
women with adequate adipose tissue who can tolerate autologous (flap)
tissue reconstructions may be candidates for reconstruction after
postmastectomy radiation therapy. In the era of managed care, the
cost of postmastectomy radiation also is a potential disadvantage.
Although this is an evolving research field, in 1999 I believe that
women with > 10 positive lymph nodes will continue to receive
postmastectomy radio-therapy and women with 4 to 9 positive lymph
nodes will also be recommended for radiation therapy, with the
strongest recommendation made for those with higher numbers of
positive nodes. Women with one to three positive nodes will be
considered for postmastectomy radiation based, in part, on other
clinical factors, eg, surgical margins.
1. Overgaard M, Hansen PS, Overgaard J, et al: Postoperative
radiotherapy in high-risk premenopausal women with breast cancer who
receive adjuvant chemotherapy. N Engl J Med 337:949-955, 1997.
2. Overgaard M, Hansen PS, Overgaard J, et al: Randomized trial
evaluating postoperative radiotherapy in high-risk postmenopausal
breast cancer patients given adjuvant tamoxifen: Results from the
DBCG 82 c trial (abstract). Radiother Oncol 48 (suppl 1):S78, 1998.
3. Ragaz J, Jackson SM, Le N, et al: Adjuvant radiotherapy and
chemotherapy in node-positive premenopausal women with breast cancer.
N Engl J Med 337:956-962, 1997.
4. Recht A, Gray R, Davidson NE, et al: Locoregional failure 10 years
after mastectomy and adjuvant chemotherapy with or without tamoxifen
without irradiation: Experience of the Eastern Cooperative Oncology
Group. J Clin Oncol 17:1689-1700, 1999.