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Saturday, March 13, 2010

Is Watchful Waiting too Difficult?

The rise of prophylactic double mastectomy in women with increased risk of breast cancer was recently discussed in The New York Times Health section. In particular, it noted this trend amongst women with the diagnosis of unilateral ductal carcinoma in situ (DCIS), or pre-invasive breast cancer. While it has been known that in women with genetic cancer syndromes, including BRCA1 and BRCA2, double mastectomy reduces risk, the efficacy of the approach is uncertain in women with other risk profiles, yet more women and surgeons seem to be doing it.

Knowing when to test, treat and act is part of art of medical practice. The ability to convey this information effectively is also an art. Both patients and doctors may have a hard time embracing watchful waiting with respect to many forms of cancer and pre-cancer. In the case of cancer of the cervix, it is known that infection with Human Papillomavirus (HPV) is causative in cancer development. However, only a small percentage of those infected actually go on to get cancer. Low grade dysplasia, a condition that is early in the cervical cancer development continuum, frequently spontaneously resolves without treatment. Fortunately, in the case of cervical cancer, there is now a vaccine to prevent high risk HPV infection.

"Watchful waiting" has been most discussed as a treatment strategy for prostate cancer. Treatment for prostate cancer, including radical prostatectomy, is fraught with side effects that may negatively impact quality of life. The watchful waiting approach is most commonly agreed upon for older men with medical co-morbidities, or limited life expectancy. However a recent study in the New England Journal of Medicine followed men who were screened for prostate cancer with PSAs and found no mortality benefit to early detection at 10 years, calling into question the utility of screening even younger men.

In the case of breast cancer, the United States Preventive Services Task Force recently published its revised guidelines for breast cancer screening suggesting that mammography screening be delayed in most women until age 50. These recommendations were in part based on the finding of “adverse effects” resulting from overzealous screening procedures. Although breast cancer screening in women ages 40 to 50 is known to be effective for early detection, its use is associated with the detection of a range of abnormalities of the breast, which lead to further evaluations including follow-up mammograms, MRIs and biopsies. Of course, these procedures are anxiety-provoking and costly. What's more, pre-cancerous breast disease, as is true with other precancerous conditions, may not always progress to invasive cancer.

Invasive cancer of the breast arises from pre-invasive conditions of breast tissue, the most benign of which is ductal hyperplasia, followed by atypical ductal or lobular hyperplasia, followed by ductal and lobular carcinoma in situ (DCIS). Even the carcinomas in situ (considered stage 0, cancer) vary in their genetics, histological characteristics and aggressiveness. The differentiation amongst these pre-cancerous conditions may be subtle and subject to variable interpretation depending on the pathologist. The appropriate management of these conditions, once detected, remains controversial.

In the past several decades the diagnosis of pre-malignant breast disorders has grown, paralleling the increased use of screening mammography. DCIS is characterized by many of the same histological and genetic features as invasive breast cancer. In DCIS, however, no invasion through the duct basement membrane occurs. DCIS represents twenty percent of malignancy detected by mammography. Ninety percent of women in which this condition is detected are asymptomatic at the time of diagnosis. Longitudinal studies of the natural history of DCIS in untreated women suggest that 15 to 60 percent will develop breast cancer in the affected breast after 10 years. This is a broad range and at this point it is not well-understood what factors cause breast cancer to develop in some women with DCIS, while cancerous changes to regress in others.

DCIS is typically diagnosed after microcalcifications are detected on mammogram. by means of stereotactic needle biopsy. The current standard of care involves wider surgical excision of surrounding breast tissue. In 10 to 15 percent of cases invasive cancer is detected in the excised tissue. However, the impact of DCIS treatment on breast cancer mortality is unclear. In addition, there is not evidence to support the removal of an unaffected breast in cases where the DCIS is unilateral.

With medicine’s current focus on early detection and the abundance of information that it may provide, it becomes increasingly important to make sure that our remedies are not worse than our diseases. After all, as much as we may not like to hear it, we are all diseased, and in effect, pre-cancerous. “First do no harm,” is part of the Hippocratic Oath. It may be easier, and perceived as less risky, to do another test, or to recommend a treatment to a patient in lieu of engaging in a detailed discussion of risks and benefits. In many cases the risks of pre-cancerous conditions are not well delineated. I am very much in favor of using current medical technology and information to detect cancer and pre-cancer. However in doing this, both doctors and patients must question what will be done with the information that we discover, and develop comfort that watchful waiting can sometimes be a good option when abnormalities are detected.


  1. I really appreciate this column. Just who finds "watchful waiting too difficult"? In my case, it's the doctors, not the patient.

    Having recently consented to my first mammogram in 10-15 years just because my physician gave me a dirty look, I'm now faced with the whole response of modern medicine to a slightly (15%?) suspicious mammogram and ultrasound. It was difficult to negotiate a 3-month reprieve rather than a biopsy, and the surgeon told me that even if there is no change in this tiny nodule in 3 months, she will still want a biopsy. I got the sense that it was largely about the comfort level of the surgeon and radiologist, to the point that I even offered to sign a waiver.

    So I am looking for more information on doctors and centers willing to use watchful waiting and/or other means to avoid invasive biopsies whenever possible.

  2. I agree--physicians do not seem to easily advocate "watchful waiting," unless that approach has been studied or backed up by a trial or guideline of some sort. I suppose that some of that is "defensive medicine," and the other part is that we are taught to act, not to wait. In fact, like you, many patients probably prefer the watchful waiting approach, especially when they have accurate views about the risks. Just saw a patient recently who opted for this approach after surgery for testicular cancer. In fact, he disclosed to me that he left his first urologist and sought out another who was more supportive of his approach.