Small tumors are good, or good tumors are small?


The above is an abbreviation of the title of a New England Journal of Medicine (N Engl J Med 2017; 376:2286-91), in this article, the authors discuss identification of a group of tumors that are composed of predominantly overdiagnosed tumors. In order to be clear, I have to start with few definitions.

Overdiagnosis refer to tumors dectected on screening that never would have led to clinical symptoms.

Another commonly used definition in such discussion would be the lead time which is the length of time between when cancer can be detected by screening and when it would have become clinically apparent without screening. In order to understand fully the current article, I must also briefly summarize another interesting NEJM article by Welch et al in which the authors through review of SEER data, with regard to tumor size, and breast-cancer-specific mortality arrived at a conclusion that the since the introduction of screening mammography the following is noted,

  • The rate of detection of large tumors fell.
  • The rate of detection of small tumors rose.
  • The above is a result of overdiagnosis and not early detection of small tumors that was destined to become larger.
  • The reduction in breast-cancer-specific mortality since screening mammography occurred as a result of improvement in systemic therapy.

In the current study, the investigators looked at invasive breast cancer that was diagnosed in the period 2001-2013 at the surveillance, Epidemiology, and End Result (SEER) database. Patients were divided into three prognostic groups based on tumor grade, estrogen-receptor, and progesterone-receptor, details of their method is beyond the scope of this post, but a summary is provided in the following diagram.


Following the above biologic subgroups were plotted along tumor size in six groups ( 01-1, 1.1-2, 2.1-3, 3.1-4, 4.1-5, and >5cm) for patient age less than 40, and patient age more than 40. Further breast-cancer-specific survival curves by tumor size and biology ( T1 favorable, T2 favorable, T1 unfavorable, T2 unfavorable) for patient age more than 40. The following was observed,

  1. In patients ≥40 years, favorable biology was noted in 38.2% of tumors  ≤ 1, and decreased to only 9% for tumors >5cm, also unfavorable biology was 14.1% of tumors ≤1cm, and increased 35.8% for tumors >5cm.
  2. In patients <40 years, similar findings were noted, however, favorable biology was about half the above, and unfavorable biology was more common.
  3. Large tumors with favorable features had a better prognosis than smaller tumors with unfavorable biologic features.
  4. Lead time in tumors with favorable biologic profile was much longer than lead time in tumors with the unfavorable biologic profile.
  5. Overdiagnosis is less common in young women and increases with age.
  6. Tumor size depends not only on when the tumor was detected, but also depend on underlying biologic factors.

Discussion, on reviewing the current article, as well as the above-cited article by Welch et al, my conclusions are.

  • Screening mammography causes increased overdiagnosis. With many small tumors with favorable biologic factors have such excellent prognosis and do not progress to large tumors within the lifetime of the patient.
  • While the prognosis of unfavorable tumors would be improved if they are diagnosed at a smaller size i.e. less than 2 cm, however, screening mammography is less than effective in achieving that since such unfavorable tumors have short lead time.
  • The medical oncology community is now completely aware of biologic factors (including genomic assays) in determining prognosis and tailoring therapies accordingly, the new updated 8th edition of the AJCC staging classification take into account such parameters.

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Small tumors are good, or good tumors are small?