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The Contribution of Medicine to the Primary Treatment of Breast Cancer¹

Istituto Nazionale Tumori, Milan, Italy

To the young clinical oncologist, breast cancer today appears as a vast and complex discipline involving almost all the techniques and knowledge of biology, epidemiology, and therapeutics. Fifteen years ago, to an objective critic the search to improve the control of high-risk breast cancer by drug treatments could almost parallel Leonardo da Vinci's efforts to fly. Today, in spits of the vast and intrinsic biological problems we can appreciate the reality of the progress being achieved as well as its limits.

Present chemotherapy and hormonal therapy are far from being optimal adjuvant treatments. However, their somewhat empirical administration has achieved prolonged, clinically useful results. The biological and strategic significance of this observation far exceeds the results themselves. Thus, clinicians no longer have reason to believe that the primary therapy for resectable breast cancer should be confined only to the operating theater; investigators can realize that despite the expected cell resistance to single or multiple drugs, early administration of medical treatment has produced some favorable long-term results and therefore renewed respect for the importance of clinical data. It is useful to stress at this point that the time required from the introduction of potentially curative treatments for a given tumor to the recognition and confirmation that curative treatment has, in fact, been delivered is substantial. For the adjuvant therapy of breast cancer, the time lag will be much longer compared to Hodgkin's disease and testicular cancer. Also, additional time is required for the transfer of technology to the community so that a decrease in national mortality statistics can be appreciated (3).

Competing forces have continuously played a role in determining the management of breast cancer (6). Knowing this, what is important is that clear biological principles direct new approaches. At present, major creative challenges will probably be in methodology rather than in hypothesis formulation. One attractive methodology will be to measure the degree of morphological and biological alterations in the primary tumor following medical treatment administered in various forms, dosages, and duration. The search for new, potentially useful prognostic factors should be performed, in our opinion, without being obsessed by the constraint of randomized trials. Until the salient tumor variables are evaluated through controversies, dissensions, and doubts, randomization will remain the best technique in assuring that proposed treatments with new premises will be assigned without bias.

The multifaceted interests, including political and sociological ones, generated by the high frequency of breast cancer may tend to blur our research objectives. Therefore, a proper balance must be achieved between research and medical care, and, most importantly, scientific objectivity should be maintained to avoid harsh and discouraging criticisms. Admittedly, technical and conceptual difficulties may arise with the army of physicians involved in the clinical care of breast cancer, since many of them have adopted present findings as standard treatment and will therefore be reluctant to refer patients for new studies.

Many actors are now crowding the stage of breast cancer. Some are investigating new avenues of research on treatment through effective cooperation with basic scientists in an attempt to formulate meaningful hypotheses. Some are engaged in repeating on a large scale studies which have previously shown either promising or controversial results, and their goal is to refine present state of the art. Some are busy in the organization of new large cooperative groups, national or international, either to design protocols "easy to manage and which do not take up a lot of time" or to evaluate questions that are not really meaningful because of their concern that "what is good for science may not necessarily be good for the patient" (91): "O! there be players that I have seen play, and heard others praise, and that highly, not to speak it profanely, that neither having the accent of Christians nor the gait of Christian, pagan, nor man, have so strutted and bellowed. ..." (W. Shakespeare, Hamlet, Act II, Scene II). We are frightened by the possibility that these "players" will eventually occupy most of our time and engender the greatest confusion.

In conclusion, the contribution of medicine in the primary management of breast cancer rests not only on the limited but consistent reduction in the odds of death, i.e., on the possibility of saving lives, but on revealing more about the biological complexity of this disease. Also it has stimulated basic scientists and research clinicians to integrate their efforts. Further clinical progress is expected, but good action should depend on good actors.

¹ Supported in part by Contract N01-CM-07338 with the Division of Cancer Treatment, National Cancer Institute, NIH.

² To whom requests for reprints should be addressed, at Division of Medical Oncology, Istituto Nazionale Tumori, Via Venezian, 1, 20133 Milano, Italy.

Received 8/28/87. Revised 11/30/87. Accepted 1/28/88.

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