Breast Cancers with Brain Metastases


Introduction

Breast cancer is the most common carcinoma in women, accounting for 23% of all female cancers globally ( ). The etiology of breast cancer is multifactorial, involving diet, reproductive factors, and hormones. The overall incidence is higher in developed countries.

Breast carcinoma usually presents with a palpable mass, but less commonly, skin retraction, nipple inversion, nipple discharge, change in the size or shape of the breast, or a change in the color or texture of the skin may also be seen. These clinical signs are not specific and may also be seen in benign breast disease, so evaluation by radiology and pathology (triple assessment) is recommended for definitive diagnosis.

Ultrasonography is the imaging method of choice for young patients, and mammography is better for older patients because of physiologic changes of breast density with age. At mammography, breast cancer frequently manifests as an ill-defined or spiculated mass, with or without associated calcifications, or as architectural distortion, focal asymmetric density, or calcifications. At ultrasonography, breast cancer may show up as mass with internal structures or increased vascularity.

The techniques commonly used to screen breast mass include fine-needle aspiration cytology (FNAC) or core-needle biopsy (CNB). FNAC is much simpler to perform and has very high sensitivity and accuracy. Compared to the more expensive and time-consuming CNB, FNAC has limited ability in confirming invasion in a breast cancer. Typing of breast cancer is usually based on histology, with specific histotypes showing characteristic prognostic implication. The molecular classification, although being based on gene expression profiling, also shows moderately specific histologic characteristics in some of the molecular subgroups.

Breast cancer is staged using the TNM classification, which is based on tumor extent (T), lymph node status (N), and metastases (M) (AJCC Cancer Staging Manual, 7th ed.). The T, N, and M are combined to create five stages (0, I, II, III, IV) that summarize the extent of regional disease and provide guidance to local disease control as well as to determine the value of systemic therapy.

Approximately 10–15% of breast cancer patients develop metastases within 3 years after initial diagnosis; however, a time lapse of 10 years or more for metastases at distant sites after initial diagnosis is also not unusual ( ). The most common metastatic sites are bone, lung, and liver ( ).

Of all metastatic carcinomas to the brain, breast cancer is the second most common cause after lung cancer. The overall incidence of central nervous system (CNS) metastasis is about 10–15% in all patients with breast cancer ( ), and about 10–16% are Stage IV breast cancer patients. In autopsy series, about 30% of breast cancer patients harbor CNS metastases ( ). The incidence of brain metastases is increasing, probably because of the introduction of more sensitive and accurate diagnostic methods for detecting brain metastases, and the development of improved adjuvant and palliative therapy regimens, leading to improvements in long-term survival of breast cancer patients. Prolonged survival means a higher chance of experiencing late complications. As the median time from diagnosis of cancer to the occurrence of brain metastases either to the brain parenchyma or to the leptomeninges is longer in cases of breast cancer compared to other cancers, usually 2–3 years ( ), there is also an increased number of patients who could live long enough for brain metastases to develop. Cerebrum is the most common parenchymal site of metastases, followed by cerebellum and brainstem. Evidence indicates that the frequency of brain metastases, ranging from 6% to 46%, may be higher among women with triple negative (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2] negative) breast cancers (TNBC) than in other breast tumor subtypes ( ; ; ).

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