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Nature Reviews Clinical Oncology published online 23 July 2013; doi:10.1038/nrclinonc.2012.126-c3

CORRESPONDENCE

The letter of Lyratzopoulos and Abel (Earlier diagnosis of breast cancer: focus‑ing on symptomatic women. Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2012.126‑c1)1 discusses the possibility that interventions other than mammography screening (as covered in our article [Viewpoint: Breast cancer screening: the questions answered. Nat. Rev. Clin. Oncol. 9, 599–605; 2012]2) could contribute to reducing symptomatic breast cancer.1 Symptomatic cancer often equates to late‑stage cancer at diagnosis, and screening is deemed to reduce breast cancer mortality thanks to detecting cancer at an early stage, before it causes symptoms. Lyratzopoulos and Abel posit that ‘breast awareness’ could be a major tool for redu‑cing patient’s delay—that is, the amount of time between first symptoms and diagnosis especi ally in women in age groups not eli‑gible for screening, and in women belonging to low socioeconomic groups who are less inclined to attend screening. In other words, ‘breast awareness’ could complement the job done by mammography screening.

A wealth of epidemiological data show that in most Western Europe, US and Australian populations, the incidence of advanced‑stage breast cancer has remained fairly stable over the past 20 to 30 years, even in areas where mammography screening has been in place for 15 to 30 years and where participation in screening is 70% or more.3–7 More surpris‑ing, practically no decline has been observed in the incidence of cancer diagnosed when metastases have already spread in distant organs (that is, stage IV cancers). In this regard, the epidemiological data do not provide evidence that breast cancer screen‑ing has influenced the incidence of symp‑tomatic cancer, which means that the burden of symptomatic breast cancer is about same today as it was before the introduction of mammography screening. Recommendation of mammography screening is mainly justi‑fied by randomized trials that showed the ability of periodic mammography screening

REPLY

Mammography screening and women with symptomatic breast cancerPhilippe Autier

to reduce breast cancer mortality.8,9 In these trials, reduction in the risk of breast cancer‑ related death was directly correlated with the risk of being diagnosed with an advanced‑stage cancer.10 Hence, the ability of screen‑ing to reduce the risk of breast cancer death is tightly dependent on its ability to decrease the risk of advanced‑stage cancer. Considering this strong connection between change in risks and the absent or limited reductions in the incidence of advanced‑stage cancer in well‑screened populations implies that nationwide mammography screening programmes would have limited influence on breast cancer mortality. The reason why there is such a discrepancy between results of randomized trials and epidemiological data is not known. One clue is that in random‑ized trials that found an association between screening and mortality reduction, women in control groups (as well as their family and doctor) ignored that they were part of a trial (the so‑called left‑to‑nature trial design). Therefore, women in intervention groups received much more attention and informa‑tion than women in control groups. Hence, as some authors have suggested,11 breast awareness could have translated into earlier detection of cancers not detected by screen‑ing (that is, interval cancers and cancers among women not attending screening), which would have contributed to reductions in breast cancer mortality. This hypothesis is supported by observational studies that showed a correlation between first symptoms and visit to a doctor with cancer stage.12,13 But, it remains to be demonstrated that increasing awareness might actually contrib‑ute to reducing the incidence of symptomatic cancer. The way ahead is probably to verify the potential of ‘breast awareness’ though intervention studies.

International Prevention Research Institute (iPRI) and Strathclyde Institute of Global Public Health at iPRI, Espace Européen, Bâtiment G, Chemin du Saquin, 69130 Ecully, Lyon, France. philippe.autier@i-pri.org

Competing interestsThe author declares no competing interests.

1. Lyratzopoulos, G. & Abel, G. Earlier diagnosis of breast cancer: focusing on symptomatic women. Nat. Rev. Clin. Oncol. http:// dx.doi.org/10.1038/nrclinonc.2012.126-c1.

2. Autier, P., Esserman, L. J., Flowers, C. I. & Houssami, N. Breast cancer screening: the questions answered. Nat. Rev. Clin. Oncol. 9, 599–605 (2012).

3. Autier, P. et al. Advanced breast cancer incidence following population-based mammographic screening. Ann. Oncol. 22, 1726–1735 (2011).

4. Autier, P. & Boniol, M. The incidence of advanced breast cancer in the West Midlands, United Kingdom. Eur. J. Cancer Prev. 21, 217–221 (2012).

5. Nederend, J. et al. Trends in incidence and detection of advanced breast cancer at biennial screening mammography in The Netherlands: a population based study. Breast Cancer Res. 14, R10 (2012).

6. Kalager, M., Adami, H. O., Bretthauer, M. & Tamimi, R. M. Overdiagnosis of invasive breast cancer due to mammography screening: results from the Norwegian screening program. Ann. Intern. Med. 156, 491–499 (2012).

7. Bleyer, A. & Welch, H. G. Effects of three decades of screening mammography on breast-cancer incidence. N. Engl. J. Med. 367, 1998–2005 (2012).

8. Vainio, H. & Bianchini, F. (Eds) IARC Handbooks of Cancer Prevention. Vol. 7. Breast Cancer Screening (IARC Press, Lyon, 2002).

9. Humphrey, L. L., Helfand, M., Chan, B. K. & Woolf, S. H. Breast cancer screening: a summary of the evidence for the U. S. Preventive Services Task Force. Ann. Intern. Med. 137, 347–360 (2002).

10. Autier, P., Héry, C., Haukka, J., Boniol, M. & Byrnes, G. Advanced breast cancer and breast cancer mortality in randomized controlled trials on mammography screening. J. Clin. Oncol. 27, 5919–5923 (2009).

11. Bleyer, A. & Welch, H. G. Effect of screening mammography on breast cancer incidence. N. Engl. J. Med. 368, 679 (2013).

12. Richards, M. A., Westcombe, A. M., Love, S. B., Littlejohns, P. & Ramirez, A. J. Influence of delay on survival in patients with breast cancer: a systematic review. Lancet 353, 1119–1126 (1999).

13. Arndt, V. et al. Patient delay and stage of diagnosis among breast cancer patients in Germany—a population based study. Br. J. Cancer 86, 1034–1040 (2003).

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