Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer

Abstract

Trastuzumab is an effective treatment for patients with metastatic breast cancer (MBC) that overexpresses HER-2. A high incidence of brain metastases (BM) has been noted in patients receiving trastuzumab. A retrospective chart review was conducted of 100 patients commencing trastuzumab for metastatic breast cancer from July 1999 to December 2002, at the Christie Hospital. Seven patients were excluded; five patients developed central nervous system metastases prior to starting trastuzumab, and inadequate data were available for two. Out of the remaining 93 patients, 23 (25%) have developed BM to date. In all, 46 patients have died, and of these 18 (39%) have been diagnosed with BM prior to death. Of the 23 patients developing BM, 18 (78%) were hormone receptor negative and 18 (78%) had visceral disease. Univariate analysis showed a significant association between the development of cerebral disease and both hormone receptor status and the presence of visceral disease. In conclusion, a high proportion of patients with MBC treated with trastuzumab develop symptomatic cerebral metastases. HER-2-positive breast cancer may have a predilection for the brain, or trastuzumab therapy may change the disease pattern by prolonging survival. New strategies to address this problem require investigation in this group of patients.

Risk factors for brain relapse in HER2-positive metastatic breast cancer patients

“…Cumulative 3-year risk of brain relapse of 42% is in the range found in other series of HER2-positive advanced breast cancer patients [11][12][13][14][15][16][17]23]. In this cohort the average annual risk of symptomatic brain relapse for surviving patients during consecutive 7 years of follow-up was 10%, with no apparent plateau.…”

“…The small number of patients not administered trastuzumab calls for cautious interpretation of this result, nevertheless resistance of brain lesions to trastuzumab therapy was consistently reported by others. Notably, several studies demonstrated the development of brain metastases despite the response to trastuzumab in extracranial sites, and no prophylactic effect of trastuzumab on brain relapse both in advanced disease and in the adjuvant setting [11][12][13][14][15][16][17]. Brain is the sole site of progression in about 10% of advanced breast cancer patients administered trastuzumab [16].…”

“…Currently HER2-positive breast cancer patients are managed with trastuzumab, a monoclonal antibody against extracellular domain of HER2 receptor. Trastuzumab does not cross through the blood-brain barrier and is ineffective in preventing and treating brain lesions [11][12][13][14][15][16][17]. Recently, Food and Drug Administration (FDA) and European Medicines Agency (EMEA) granted approval to lapatinib, an anti-HER2 small-molecule tyrosine kinase inhibitor, for use in women with advanced HER2-positive breast cancer who have progressed on trastuzumab treatment.…”

Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer

“…2,3,5,6 In addition, the higher incidence may be caused by clonal selection induced by novel therapeutic agents like Herceptin. [7][8][9][10] Because diagnostic imaging procedures will usually only be performed after clinical symptoms have become manifest, identification of risk factors for CNS involvement could enable specific surveillance and management of patients at risk. Indicators of an increased risk for CNS metastases have been described such as young age at diagnosis, diseasefree interval less than 1 year, oestrogen receptor (ER) or progesterone receptor (PR) negativity, 11 and Her-2/neu amplification.…”

Czy u chorych na HER2-dodatniego raka piersi z przerzutem do mózgu rozpoznanym w trakcie leczenia trastuzumabem należy zmienić lek? Głos na TAK

“…Z drugiej strony w rejestrze prowincji Parma czas do pojawienia się przerzutów do mózgu u chorych na HER2--dodatniego raka leczonych i nieleczonych trastuzumabem wynosił odpowiednio 20,3 i 10,3 miesiąca (p = 0,018), co wynika jednak z aktywności tego leku poza ośrodkowym układem nerwowym [3]. Z kolei u chorych na HER2-dodatniego, zaawansowanego raka piersi skumulowane ryzyko wystąpienia objawowych przerzutów do mózgu szacuje się na 10-40% [3,[5][6][7][8][9][10][11][12][13][14], a średnie roczne ryzyko na około 10% [14]. Podobnie jak w leczeniu uzupełniającym, leczenie trastuzumabem w rozsianym raku piersi znacząco opóźnia ujawnienie się objawowych przerzutów do mózgu (w badaniu Dawood i wsp.…”