Gambacorti-Passerini C, Tornaghi L, Cavagnini F, Rossi P,
Pecori-Giraldi F, Mariani L, et al. Gynaecomastia in men
with chronic myeloid leukaemia after imatinib. Lancet 2003;
361:1954 – 1956.

As Dr Baccarani reported, there were reports from a number of years ago about this phenomenon. Subsequently we reported a case of unusual fluid retention in breast tissue in women (Ostro D, Lipton JH (2007) Unusual Fluid Retention with Imatinib Therapy for Chronic Myeloid Leukemia. Leuk Lymph 48: 195-6)

I think the first case series above looks at a number of endocrinologic aspects of the work up that should be considered. It is however necessary to distinguish between legitimate gynecomastia and unusal manifestations of fluid retention.

If it turns out to be imatinib related, then the only therapy if disconcerting enough, but be a switch in medications. In the case of the fluid retention, we did not find that aggressive diuretic therapy was effective. In fact the patient in question, went on to cosmetic breast reduction therapy, and then recurred as would be expected, post surgery, a phenomenon that has been reported with blepheroplasty under similar circumstances.

It is impossible to establish the frequency of gynecomastia during TKIs treatment, but since there are no reports (as far as I remember, but Dr. Perez can do a medline) I presume that gynecomastia is a very rare adverse event. Please remember that since the average patient with CML is male and has a median age of 55 to 60 years, some patients will develop gynecomastia irrespective of treatment.
Having said that, it may be relevant to remember that there are few, unconfirmed reports, of a decrease of testosterone and of fertility in male patients. But again, the frequency (unknown) should be compared with the frequency of the same findings in a control population. There are several reports of a “second” malignancy in CML patients treated by TKI, but breast cancer incidence was not recorded.
From a practical point of view, in case of clinically significant gynecomastia, a study of the appropriate hormones and an ultrasound examination of breast are advised. If the patient is in stable deep molecular response it may be possible to discontinue treatment for few weeks with careful molecular monitoring, to see if treatment discontinuation has any effect on gynecomastia. But only in case of very stable and very deep response, because in these cases we know that if after discontinuation there is a molecular relapse, the molecular response will be achieved again upon retreatment. In any other case, the TKI should not be discontinued.

I wiil ask about frecuency and management the patients with gynecomastia with Imatinib or Dasatinib