This Article Full Text Full Text (PDF) All Versions of this Article: theoncologist.2008-0162v1 13/11/1137    most recent eLetters: Submit a response to this article Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Berruti, A. Articles by Bottini, A. Search for Related Content PubMed PubMed Citation Articles by Berruti, A. Articles by Bottini, A.

The Community Oncologist

Presurgical Systemic Treatment of Nonmetastatic Breast Cancer: Facts and Open Questions

^aOncologia Medica, Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Azienda Ospedaliera Universitaria San Luigi, Orbassano, Italy; ^bUnità di Patologia Mammaria – Breast Cancer Unit, Azienda Instituti Ospitalieri di Cremona, Cremona, Italy; ^cOncologia Medica, Ospedale di Carmagnola, Carmagnola, Italy; ^dDipartimento di Epidemiologia Clinica, Istituto Nazionale per la Ricerca contro il Cancro, Genova, Italy

Key Words. Primary systemic treatment • Pathological complete response • Breast cancer • Surrogacy

Correspondence: Alfredo Berruti, M.D., Oncologia Medica, Azienda Ospedaliera Universitaria San Luigi di Orbassano, Regione Gonzole 10, 10043 Orbassano, Italy. Telephone: 39-011-9026512; Fax: 39-011-9026992; e-mail: alfredo.berruti{at}gmail.com

Received July 29, 2008; accepted for publication September 30, 2008; first published online in THE ONCOLOGIST Express on November 7, 2008.

Disclosure: The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or staff managers.

There are several advantages of administering primary systemic therapy (PST) instead of adjuvant therapy in the management of early breast cancer patients: (a) PST allows for a quantifiable evaluation of the sensitivity or resistance of any treated case and (b) the response assessment offers the opportunity to "cross over" to a different regimen for an individual patient, leading to more flexible, "tailored" therapies. Indeed, these advantages are tenable if one assumes that the primary tumor response serves as a surrogate marker of the efficacy of PST in terms of survival. Unfortunately, this has not yet been validated. The data that are actually available show that both clinical complete response (cCR) and pathological (p)CR have prognostic significance. pCR after chemotherapy has a greater prognostic impact than cCR; however, it is frequently observed in a subset of tumors—such as those that are estrogen receptor negative, are human epidermal growth factor receptor positive, and have elevated proliferative activity—but occurs rarely in their human epidermal growth factor receptor-2/neu counterparts. cCR is more sensitive than pCR, but its assessment presents many hindrances. cCR after chemotherapy can predict early on which tumors are destined to undergo pCR, suggesting a role for this endpoint guiding further treatment decisions early on. The pCR rate in small randomized PST studies comparing chemotherapy with chemotherapy plus trastuzumab was able to predict the difference in survival observed in large, randomized adjuvant trials with a similar study design. Conversely pCR cannot predict the outcome benefit of patients undergoing different hormonal therapies.

In conclusion, pCR may be a reliable surrogate endpoint for PST efficacy in a subset of patients undergoing chemotherapy.