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© Borgis - Postępy Nauk Medycznych 2/2011, s. 126-130
*Elżbieta Senkus, Jacek Jassem
Rak piersi – stan wiedzy w 2011 roku
Breast cancer – where are we standing in 2011?
Department of Oncology and Radiotherapy, Medical University of Gdańsk
Head of Department: prof. dr hab. med. Jacek Jassem
Streszczenie
Rak piersi j jednym z najważniejszych problemów zdrowotnych i społecznych u kobiet. Dzięki upowszechnieniu programów badań przesiewowych i poprawie skuteczności leczenia, w niektórych krajach w ciągu ostatnich 20 lat udało się doprowadzić do obniżenia współczynników umieralności na ten nowotwór o około 1/3. Postępy w leczeniu raka piersi obejmują również ograniczenie niekorzystnego wpływu terapii na jakość życia chorych. Osiągane jest to głównie przez zastępowanie okaleczających procedur chirurgicznych zabiegami oszczędzającymi i rekonstrukcyjnymi. Postęp w leczeniu systemowym wiąże się przede wszystkim z osiągnięciami biologii molekularnej i lepszym zrozumieniem patomechanizmów raka piersi, w tym ze zidentyfikowaniem podtypów molekularnych raka piersi przy pomocy badań ekspresji wielogenowej. Doprowadziło to do znaczących zmian w strategii leczenia wczesnego raka piersi poprzez zastąpienie ryzyka nawrotu jako podstawowego czynnika determinującego wybór strategii leczenia charakterystyką biologiczną nowotworu i przewidywanym prawdopodobieństwem odniesienia korzyści z poszczególnych metod leczenia. Najważniejsze osiągnięcia obejmują też wprowadzenie leków ukierunkowanych molekularnie przeciwko receptorowi HER2: trastuzumabu i lapatynibu. Rozwój terapii ukierunkowanych molekularnie oznacza nie tylko tworzenie leków „celowanych”, ale również identyfikację czynników predykcyjnych, pozwalających na wyodrębnienie chorych mających wysokie prawdopodobieństwo odpowiedzi na leczenie. Największe zainteresowanie budzi tutaj polimorfizm cytochromu P450 2D6 – enzymu uczestniczącego w metabolizmie tamoksyfenu. Prowadzone obecnie badania pozwalają mieć nadzieję na dalszą poprawę wyników leczenia i jakości życia chorych na raka piersi.
Summary
Breast cancer is one of the major health and social problems in women. Due to the wide application of screening programs and to improvements in treatment, breast cancer mortality in some countries has decreased by more than 30% over the last twenty years. Advances in breast cancer management include also the decreasing negative impact of therapy on patients? quality of life. This is mostly achieved by substituting major, mutilating surgery with organ-sparing or reconstructive procedures. The progress in systemic treatment of breast cancer is mostly related to the developments in molecular biology and a better understanding of breast cancer pathomechanisms, including identification of molecular subtypes of breast cancer by multigene assays. This has led to a profound modification of treatment strategies in early breast cancer. Failure risk has now been substituted as the main factor driving treatment decision-making by biology of tumor and likely sensitivity to particular treatment modalities. Most important achievements include also the development of trastuzumab and lapatinib – molecularly “targeted” compounds directed against HER2. Development of targeted therapy includes not only designing targeted agents but also identification of constitutive predictive features of particular patients, which may allow individual tailoring of systemic therapies. Among these, most interest is raised by polymorphisms of the cytochrome P450 2D6 – an enzyme involved in the metabolism of tamoxifen. Ongoing research will hopefully result in further improvements in prognosis and quality of life of breast cancer patients.
Breast cancer is one of the major health and social problems in women. In 2007, almost 14,500 new cases and over 5,200 breast cancer deaths were noted in Poland, making it the most frequent female malignancy and the second most common cause of cancer death (1).
Over the last years, significant progress has been made in the management of breast cancer. The most impressive data come from the United Kingdom, where more than a 1/3 relative decrease in breast cancer mortality was noted over the last twenty years (fig. 1) (2). A similar trend can also be observed in many other countries but, unfortunately, not in Poland (1). This phenomenon is mostly related to the wide application of screening programs allowing for early diagnosis of malignancy and to improvements in the treatment of breast cancer, in particular of early disease.
Fig. 1. Decrease in breast cancer mortality in United Kingdom and USA (based on) (2).
Advances in breast cancer management implemented over the last years include not only improvement of treatment outcomes but also decreasing harm of anti-cancer treatment in terms of patients? quality of life. The latter may be attributed both to technological progress and to changes in the paradigms of surgical treatment, in particular substituting major, mutilating surgery with organ-sparing or reconstructive procedures. Currently, a significant fraction of early breast cancer patients undergo breast-conserving treatment and the development of oncoplastic surgical techniques allows for an effective combination of oncological safety and good cosmesis (3, 4). Patients not amenable to breast-saving therapies may benefit from a large array of breast-reconstructive surgical techniques.
A tendency to decrease the extent of surgery also applies to axillary lymph nodes. This is exemplified by the increasing use of sentinel lymph node technology, which in node negative patients allows for the omission of axillary lymph node dissection (5). As a consequence, the risk of arm lymphedema (which is a frequent complication of axillary lymphadenectomy, in particular when followed by postoperative radiotherapy) is markedly decreased.
The progress in systemic treatment of breast cancer is mostly related to the developments in molecular biology and a better understanding of breast cancer pathomechanisms. One of the most remarkable steps was the identification of molecular subtypes of breast cancer, based on multigene assays (6). These studies showed a number of distinct molecular breast cancer subtypes (luminal A, luminal B, basal, HER2+, normal breast-like) with various clinical behavior, prognosis and response to therapy. In consequence, these subtypes are currently considered separate clinical entities. Some of the multigene assays based on gene microarray technology have become commercially available and are accepted as ancillary tools in treatment decision-making in early breast cancer (7, 8). Better understanding of tumor biology has led to a profound modification of treatment strategies in early breast cancer. In particular, failure risk (which is directly related to tumor bulk and extent) has been substituted as the main factor driving treatment decision-making by biology of tumor and probability of benefit from a particular treatment modality (9).
As a result of studies on molecular pathomechanisms, a number of new “targeted” compounds have been developed and become available for breast cancer patients. Of these, a particularly important one is trastuzumab – a humanized monoclonal antibody against HER2. HER2 is a molecule belonging to the family of epidermal growth factor receptors and its overexpression or gene amplification in breast cancer cells (assessed by immunohistochemistry or in situ hybridization, respectively) is associated with shorter disease-free and overall survival (10).
Unlike most of the targeted agents, trastuzumab, when added to standard chemotherapy, was found to provide overall survival benefit in HER2 positive metastatic breast cancer patients. In the pivotal study, the median overall survival in patients treated with chemotherapy and trastuzumab was almost five months longer than with chemotherapy alone (11). In the subsequent randomized phase II study, the difference in median overall survival between chemotherapy + trastuzumab vs chemotherapy alone arms was even greater (over eight months, p = 0.0325) (12). Trastuzumab is generally well tolerated, with the main clinically relevant toxicity being cardiac dysfunction. This side-effect was observed mostly when trastuzumab was combined with anthracyclines and, in contrast to anthracycline-related damage, it is usually reversible and probably does not lead to long term sequelae. Moreover, with proper cardiac medication, this toxicity does not preclude further treatment with trastuzumab (13).

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otrzymano: 2010-12-21
zaakceptowano do druku: 2011-01-10

Adres do korespondencji:
*Elżbieta Senkus
Katedra i Klinika Onkologii i Radioterapii Gdański Uniwersytet Medyczny
ul. Dębinki 7, 80-211 Gdańsk
tel.: +48 (58) 349-22-21, fax: +48 (58) 349-22-10
e-mail: elsenkus@gumed.edu.pl

Postępy Nauk Medycznych 2/2011
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