Etiology

​​​​In women, ovarian hormones stimulate the development of the breast, and the length of time that the breast is exposed to estrogen and progesterone influences risk.[8] Genetic and environmental factors are also involved in the etiology of breast cancer (see Primary invasive breast cancer).[9][10][11]​​

Breast cancer metastases are phenotypically different from the primary cancer and, in the majority of women who experience recurrence, are already present at the time of diagnosis.[12]​ Research to elucidate key factors that influence breast cancer recurrence is ongoing.

Bone is the most common secondary site for metastases in breast cancer patients.[13][14] The brain, liver, lungs, and lymph nodes are also common secondary sites for metastases.[13][14] Brain metastases are generally associated with more aggressive disease and shorter survival compared with metastases at other secondary sites.[14]

Approximately 99% of breast cancers occur in women, and 1% occur in men.[15]

Pathophysiology

Metastatic breast cancer (MBC) can occur de novo (i.e., present at diagnosis) or, more commonly, following relapse (recurrence) after treatment for early or locally advanced breast cancer.

MBC develops when breast cancer cells from the primary tumor disseminate to secondary sites.[16] This is a multistep process involving: cancer cells escaping from the primary tumor, local invasion, intravasation (cancer cells entering the blood and lymphatic vessels), circulation of cancer cells in the bloodstream and lymphatic system, extravasation (cancer cells exiting the circulation), and metastatic seeding at secondary sites.[12] Cell-intrinsic and cell-extrinsic factors at the site of metastasis can influence whether the disseminated breast cancer cells develop into metastatic tumors, or undergo cell death, or enter a state of tumor dormancy.[12]

Classification

Commonly accepted classification according to organ involvement[2]

Although there is no universally accepted classification, MBC is frequently grouped as follows:

  • Patients with bone- and soft tissue-only disease: generally disease in this group has a more indolent course, and survival is longer

  • Patients with visceral disease: generally disease is more aggressive and survival shorter.

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