“My daughter just had a mammogram and they found a
tumor. You can’t tell me her life was not saved. Should we just have
waited until it grew and was twice the size the next year?”
When a cancer is found on screening, the assumption is
that if any more time elapsed between the time of screening and the time it
became clinically apparent, a woman’s life would be lost.
There is, however, very little evidence to support what
seems emotionally to be true. In fact, the reason screening every 1 to 2 years
is of value is because tumors grow slowly enough for periodic screening to be
Screening has been shown to be of value in tumor types
that are slow growing, such as cervical cancer and colon cancer. The
recommended screening intervals now are every 3 years for Pap smears and every
10 years for colonoscopy.
The randomized trials demonstrate there is a relative
risk reduction from screening.
However, as H. Gilbert Welch, MD, pointed out in
a recent Archives of Internal Medicine article, this translates
into a reduction in mortality that is very small in absolute terms. By no means
are most women’s lives saved.
No scientific article has ever claimed that because a
cancer is detected by mammography, it is necessarily a life saved. Yet somehow
this has become what the community and many physicians believe.
Dr. Welch estimates that, of women diagnosed with a
cancer by screening, the chance that her life is saved is 13%. Importantly, the
screening trials were conducted before the use of any kind of adjuvant therapy.
In fact, the kind of adjuvant treatment we use today makes up for two-thirds of
the benefit previously attributed to screening, suggesting the chance that a
woman’s life is saved by virtue of having a screen-detected cancer is
closer to 4%.
So how could this be?
The answer lies in understanding the biology of breast
We now know that breast cancer is not one disease. Every
breast cancer detected is not a killer cancer. In fact, most of the cancers
found by mammographic screening are likely to be the ones that grow more
slowly, and many will be indolent.
Because we understand that biology should dictate
treatment, even when these tumors grow a bit bigger, treatment likely would be
the same, as will be the outcome.
Again, emerging molecular tools such as Oncotype DX and
MammaPrint allow us to assign therapy based on biology rather than tumor size.
In fact, almost 70% of the tumors mammographically
detected in women aged 50 to 60 years will be biologically low risk based on
the MammaPrint profile, half of which fit an ultralow risk or IDLE profile.
Many such tumors — if found the following year
based on screening or by symptoms — would change little or not at all, and
the timing would have little, if any, impact on outcome. This is because the
biology of the tumor would not have changed, even though the tumor may have
grown in size in the interim.
In contrast, the most aggressive breast cancers grow
quickly and often present between normal screening exams — so-called
For these tumors, screening will make little or no
difference in the type of treatment, as the aggressive biology dictates the
treatment rather than tumor size, and outcome depends mostly on response to
These tumors often are hormone receptor-negative and/or
HER-2/neu receptor-positive, although some hormone receptor-positive tumors
exhibit aggressive features as well. Treatment for these tumors will be
aggressive, regardless of size. The answer to improving outcome for women with
the most aggressive tumors is to identify better therapeutic options.
Data now show that screening every 2 years does not
result in any statistical difference in the number of more advanced cancers.
Indeed, Finnish researchers have shown that screening every 3 years is as good
as screening every year even for a woman in her 40s.
However, less screening results in fewer unnecessary
biopsies and recalls. If we are more cognizant that screening mammography
primarily helps to identify slower-growing cancers, we will be less anxious to
recall women for very low-risk marginal findings. We also can use mammography
more appropriately and reduce overtreatment, and the burden of screening on
Laura Esserman, MD, MBA, is director of the Carol
Franc Buck Breast Care Center and co-leader of the Breast Oncology Program at
the University of California, San Francisco, Helen Diller Family Comprehensive
Cancer Center. Disclosure: Dr. Esserman reports no relevant financial
For more information:
- Berry DA. N Engl J Med. 2005;353:1784-1792.
- Esserman LJ. Breast Cancer Res Treat.
- Esserman L. JAMA. 2009;302:1685-1692.
- Esserman L. J Natl Cancer Inst. 2010;102:582-583.
- Hubbard RA. Ann Intern Med. 2011;155:481-492.
- Kalager M. N Engl J Med. 2010;363:1203-1210.
- Lin C. Breast Cancer Res Treat. 2011;epub ahead of
- Paik S. N Engl J Med. 2004;351:2817-2826.
- Paik S. J Clin Oncol. 2006;24:3726-3734.
- Parvinen I. Br J Cancer. 2011;105:1388-1391.
- van’t Veer LJ. Nature. 2002;415:530-536
- van de Vijver MJ. N Engl J Med. 2002; 347:1999-2009.
- Welch HG. Arch Intern Med. 2011;epub ahead of print.
- Welch HG. J Natl Cancer Inst. 2010;102:605-613.