Women over the age of 65 who take combined oestrogen and progestogen hormone
replacement therapy (HRT) for five to 15 years or moreface a 100%
increase in the risk of developing breast cancer,regardless of their
pattern of progestogen use, says a newstudy (JAMA 2003;289: 3254-63[Abstract/Free Full Text]).
Although it had been shown previouslywith the early closingof an
arm of the Women's Health Initiative studythatwomen taking the
combined therapy have an increased risk ofbreast cancer (BMJ 2002;325: 61[Free Full Text]), data on
the long termuse of the therapy and on the risks associated with
patternsof use have been lacking.
The new study was undertaken to fill that gap. It involved 975
women aged 65 to 79 who had been given a diagnosis of invasivebreast
cancer between 1 April 1997 and 31 May 1999 in threecounties in
western Washington state.
Dr Christopher Li, the lead author and an assistant member ofthe
public health sciences division of the Fred HutchinsonCancer
Research Center, Seattle, said, "We found that longterm use of
combined oestrogen and progestin hormone replacementtherapy not only
doubles cancer risk but that the magnitudeof this risk increases
with duration of use.
"Few studies have assessed whether sequential progestin useis
related to breast cancer risk, although some studies havesuggested
that continuous use of progestin is more stronglyassociated with
breast cancer risk than sequential use. Inthis study we found that
both regimens were associated withsimilar increases in breast cancer
risk. There does not seem to be any advantage to sequential progestin use
compared tocontinuous progestin use with respect to reducing this
risk."
The researchers assessed the effect of combined hormone replacementtherapy on the risk of specific types of breast cancer. Among
their findings was that the risk of invasive lobular breastcancer
increased by 170%. This is the second most common histologicaltype
of breast cancer, affecting the lobes in the breast thatcontain milk
producing glands. Lobular cancer accounts for 10% to 15% of cancer cases, and
its incidence has increased by 65%in the United States during the
last 12 years, which Dr Lisays may be partly accounted for by
greater use of combinedhormone replacement therapy. The risk of
ductal breast cancerincreased by 50%. This type, involving the ducts
that carrymilk from the lobules to the nipple, accounts for about
80%of all cases of breast cancer. Women who took the combinedtherapy had twice the risk of hormone receptor positive breast
cancer, which requires oestrogen or progesterone to grow. Abouttwo
thirds of all breast cancers are either oestrogen receptor positive or
progesterone receptor positive.
Dr Li said that the study's finding that combined hormone replacement therapy
increased only the risk of hormonally positive tumoursshows the
importance of progesterone in the development ofbreast cancer.
"It appears that hormone replacement therapy must contain progesteroneto promote breast cancer growth and that it may act through stimulation of
both oestrogen and progesterone receptors, notjust one or the
other," he said.
A potential clinical implication is the need for developmentof
chemotherapeutic agents that target progesterone receptorssimilarto
the way that tamoxifen is used to treat oestrogen receptorpositive
tumours by blocking the oestrogen pathway.
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