Reply to J. Shields-Botella

We would like to thank Dr. Shields-Botella for her extensive ”Letter to the Editor“ referring to our publication. Dr. Shields-Botella summarised her own additional data on the effect of other progestins on the proliferation of human breast cancer cells. Using similar techniques and conditions to those in our investigations, her results with other human breast cancer cell lines such as T47D indicate that progestins may indeed differ in their proliferative behaviour. Of special interest were the results obtained with the 19-nor-T derivative, nomegestrol acetate (NOMAC). Unfortunately, we were not able to compare this substance with the other progestins that we have tested under our experimental conditions.

Indeed, it seems to be prudent to classify the progestins into three different classes as suggested by Dr. Shields-Botella. However, as to whether the different progestins may influence breast cancer risk in a different way remains unclear. A recent French study [1] using transdermal estradiol and different progestins (mostly progesterone) but not MPA did not indicate any breast cancer risk increase after a follow-up of about 8 years. Thus, clinical studies are urgently needed to support further the opinion that progestins are responsible for the breast cancer risk increase as observed in randomised controlled trials such as WHI [2] and Million Women study [3]. Furthermore, clinical studies are needed to identify the kind of progestins, if any, that might not increase breast risk when combined with estrogens.

So far, in vitro investigations with human breast cancer cells are a helpful experimental tool in comparing cell actions of different substances of a drug class, and may help to explore biochemical mechanisms.

References

• 1 De Lignieres B, de Vathaire F, Fournier S, Urbinelli R, Allaert F, Le M G, Kuttenn F. Combined hormone replacement therapy and risk of breast cancer in a French cohort study of 3.175 women.  Climacteric. 2002;  5 332-340
• 2 Writing Group for the Women’s Health Initiative Investigators . Risks and Benefits of estrogen plus progestin in healthy postmenopausal women.  JAMA. 2002;  288 321-333
• 3 Million Women Study Collaborators . Breast cancer and hormone-replacement therapy in the Million Women Study.  Lancet. 2003;  363 419-427