Breast cancer mortality in 500 000 women with early invasive breast cancer diagnosed in England, 1993-2015: population based observational cohort study

Dear Editor

Taylor and colleagues [1] have published an interesting paper on the prognosis of early-stage breast cancer diagnosed in England in 1993-2015 and concluded that “The prognosis for women with early invasive breast cancer has improved substantially since the 1990s”. It is not obvious that the prognosis has improved substantially, because overdiagnosis bias (which is including both lead time bias and length time bias) has not been properly accounted for, I think.

The authors use the term mortality to describe survival after a breast cancer diagnosis. Usually, mortality is being used about number of deaths per 100,000 individuals at risk of death. I do not find any reference to exposure years of the population at risk in this paper, so it looks like the authors are studying mortality (or survival) after a diagnosis rather than mortality as normally defined in epidemiology. Survival after a diagnosis is a valid measure for comparing cancer therapies in randomized trials; however, changes in 5-year survival after a diagnosis over time bear little relationship to changes in cancer mortality per 100,000 at risk. Instead, changes in 5-year survival appears primarily related to changing patterns of diagnosis [2]. The changing in patterns of breast cancer diagnosis is termed overdiagnosis (defined as the detection of tumours that would never become clinical disease during the patients’ lifetime) [3].

The level of overdiagnosis when screening for breast cancer, was typically around 50 percent 20 years ago [3]. Overdiagnosis is not only restricted to screening per se but also related to the introduction of diagnostic methods with improved sensitivity, methods which are also used outside public screening programs. Mammography also detects many ductal carcinoma in-situ (DCIS), which many think is a premalignant lesion. If true, this should lead to less invasive breast cancer being detected, which has never been observed. The level of overdiagnosis is increasing over time due the introduction of new diagnostic methods with higher sensitivity [4] and so is the level of DCIS too. Invasive breast cancer and DCIS are positively correlated and not negatively correlated.

Suppose the level of overdiagnosis is 50 percent over a time period, there is no improvement in cancer treatment and the 5-year survival was 80 percent for early-stage breast cancer at the beginning of the period. Then the number of deaths among women diagnosed with breast cancer would decline from 20 per 100 breast cancer cases to 20 per 150 breast cancer cases – a reduction by 1/3 even when there is no improvement in breast cancer treatment.

References
1. Taylor C, McGale P, Probert J, Broggio J, Charman J, et al. Breast cancer mortality in 500 000 women with early invasive breast cancer in England, 1993-2015: population based observational cohort study. BMJ 2023; 381 e074684.
2. Welch HG, Schwartz LM, Woloshin S. Are increasing 5-year survival rates evidence of success against cancer? JAMA 2000; 283: 2975-8.
3. Zahl P-H, Strand BH, Mæhlen J. Breast cancer incidence in Norway and Sweden during introduction of nation-wide screening: prospective cohort study. BMJ 2004; 328: 921-4.
4. Bakker MF, de Lange SV, Pijnappel RM, Mann RM, Peeters PHM, et al. Supplemental MRI Screening for Women with Extremely Dense Breast Tissue. NEJM 2019; 381: 2091-102