A failure analysis of invasive breast cancer: Most deaths from disease occur in women not regularly screened

Authors


The recent article by Webb et al[1] deserves comment because it does not address the limits of their study on the highly controversial argument regarding the (non)usefulness of breast cancer screening in saving lives. First, we have no comparison between the characteristics of the 7301 patients in their study and of their cancers and the rest of the patients in Massachusetts. These 2 hospitals are the flagship institutions in the state and are referral centers for women at hereditary risk (including BRCA), in whom breast cancer occurs more often before age 50 years and is more fatal. This means that there is a probable bias toward more highly aggressive cases occurring in young women. Second, a key point is the age distribution: 11% and 26% of the 7301 women with breast cancer in the study by Webb et al were aged < 40 years or aged 40 years to 49 years, respectively.[1] These percentages are 5% and 17%, respectively, in the United States.[2] Knowing that very few women are screened before age 40 years and relatively few undergo screening between the ages of 40 years and 49 years, and knowing that the mortality rate for breast cancers detected in patients aged < 50 years is much higher than that for tumors diagnosed among patients aged ≥ 50 years (13% vs 7% according to Table 4 in the study by Webb et al[1]), there is distortion in the results favoring a higher number of women screened with a good-prognosis tumor. Third, no information regarding the detection mode of these 7301 cancers was reported for patients with stage IV cancers (How have they been detected? What is the screening interval? How many women have never participated in screening?) (this figure would have been interesting because we now know that screening did not affect the incidence of metastatic cancers at the time of diagnosis[3, 4]), and a high number of deaths (436 deaths) were excluded from the study, representing approximately one-fifth of the total. Fourth, “off-program” cancers occurred among women who had undergone their last screening between 2 years and 7 years previously (median, 3.5 years), which corresponds nearly to the screening delay program in the United Kingdom. These women are not “not detected” but are screened with a longer interval. Fifth, overdiagnosis of nonprogressive tumors was likely among surviving women who were diagnosed after mammography screening, whereas it was not possible for women who died of breast cancer. It would explain the low rate of screening in this group, independent of any benefit due to early diagnosis. Last but not least, some of the authors did not declare their conflicts of interest. Daniel Kopans, for example, is the inventor of several devices and systems in the field of breast imaging and tumor location,[5] and is currently the owner or co-owner of 8 patents[6] and also serves as member of the Scientific Advisory Board of the company Dexela,[7] which is involved in breast cancer diagnosis.[8] This is a serious issue: a previous article defending mammography screening[9] was flawed because of conflicts of interest that were not formally declared. It appears possible, if not probable, that apparent survival from disease among screened women might be due to multiple and uncontrollable bias and overdiagnosis. For all these reasons, the study by Webb et al[1] does not prove that screening, nor screening at a younger age, could have saved lives.

FUNDING SUPPORT

No specific funding was disclosed.

CONFLICT OF INTEREST DISCLOSURES

The authors made no disclosures.

  • Jean Pierre Spinosa, MD

  • Faculty of Medicine University of Lausanne Lausanne, Switzerland

  • Catherine Riva

  • Winterthur, Switzerland

  • Philippe Autier, MD

  • International Prevention Research Institute Strathclyde Institute for Global Public Health Lyon, France

  • Philippe Nicot, MD

  • Panazol, France

  • Bernard Junod, MD

  • La Maison Neuve La Chapelle des Fougeretz, France