Systemic control of cerebral metastases in a patient with HER2-positive metastatic breast cancer. Clinical case

Symptomatic central nervous system (CNS) metastases are diagnosed in 10–16% of patients with metastatic breast cancer (BC). Half of all these cases are HER2-positive. At present, there are no generally accepted algorithms regarding the combination and sequence of local and systemic treatment options for these patients. According to current guidelines, different local management options remain one of the main treatment methods of brain metastases control. When local treatment is limited, patients with HER2-positive BC with СNS metastases can receive anti-HER2 therapy in combination with chemo- or hormonal therapy (for luminal tumors) or as single option. Trastuzumab poorly penetrates the blood-brain barrier, but trastuzumab-based treatment schedules increase the life expectancy in patients with HER2-positive BC with CNS metastases mainly due to control of extracranial metastases. Lapatinib, by contrast, penetrates the blood-brain barrier well, and its combination with capecitabine achieves response in heavily pretreated patients, especially in those who have central nervous system metastases as the only site of disease progression.

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Effect of Central Nervous System Metastases on Treatment Discontinuation and Survival in Older Women Receiving Trastuzumab for Metastatic Breast Cancer

Journal of Cancer Epidemiology ◽

10.1155/2012/819210 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Mark D. Danese ◽

Karla Lindquist ◽

Justin Doan ◽

Deepa Lalla ◽

Melissa Brammer ◽

...

Keyword(s):

Breast Cancer ◽

Central Nervous System ◽

Nervous System ◽

Metastatic Breast Cancer ◽

Proportional Hazards ◽

Metastatic Breast ◽

Cns Metastases ◽

Her2 Positive ◽

Time To Death ◽

Risk Of Death

Background. Trastuzumab improves survival in HER2-positive women with metastatic breast cancer (MBC). The consequences of longer survival include a higher likelihood of additional metastases, including those in the central nervous system (CNS). The effect of CNS metastases on both trastuzumab discontinuation and survival in older patients has not been described.Patients and Methods. We used the Surveillance Epidemiology and End Results (SEER) Medicare data to identify a cohort of 562 women age 66 or older with MBC who were diagnosed between January 1, 2000 and December 31, 2005, free of CNS metastases, and initiated trastuzumab after MBC diagnosis. Time to discontinuation and time to death were analyzed using proportional hazards models.Results. Newly diagnosed CNS metastases were associated with both higher risk of trastuzumab discontinuation (relative hazard[RH]=1.78, 95% CI 1.11–2.87) and higher risk of death (RH=2.49, 95% CI 1.84–3.37). The incidence rate of new CNS metastases was comparable among various sites of metastasis (10.7 to 14.7 per 1,000 patient-months), except for bone which was higher (24.1 per 1,000).Conclusion. The diagnosis of CNS metastases was associated with an increase in both the likelihood of discontinuing trastuzumab therapy as well as the risk of death.

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