Metastatic Breast Cancer Treatment Options

Breast cancer occurs when the cells of breast tissue become damaged and reproduce in an uncontrolled fashion. Metastatic breast cancer, also known as stage IV, is characterized by a malignancy that began in the breast tissue that has grown and spread, invading distant organs including but not limited to bone, lung, and liver tissues.

Excluding skin cancer, breast cancer is the most commonly diagnosed type of malignancy among U.S. women. 2019 estimates suggest that more than 265,000 women will be diagnosed with breast cancer this year and about 6% of those cases will begin as metastatic breast cancer.

It’s far more common for metastases to develop several months or years after treatment has been completed. This condition is sometimes called distant recurrence. Factors that influence distant recurrence include the biological characteristics of the original malignancy, the stage, and development of the original malignancy, and treatment strategy of the original malignancy.

Treatment Overview and Therapies

Treatment of metastasized cancers involves methods designed to eradicate the type of malignancy from which the metastases originated. For example, although breast cancer may metastasize to the bone tissue, it is not treated with the same methods as a “bone cancer” or osteosarcoma would be treated.

Unfortunately, as of this writing, metastatic breast cancer is incurable; treatments are usually staged or combined in “lines” to maximize effectiveness over time. While less advanced breast cancer cases in the U.S. are associated with an upwards of 80% 5-year survival rate, once the malignancy has spread to other tissues, it becomes almost impossible to eliminate, and the 5-year survival rate drops to only 27%.

Due to the unrelenting nature of the disease, metastatic breast cancer treatment plans focus on creating the highest potential for the longest survival possible, with the fewest side-effects, thus encouraging the best quality of life for the patient.

Many factors will influence the treatment plan for metastatic breast cancer including:

• The type and developmental stage of the original malignancy
• Hormone receptor and/or human epidermal growth factor receptor 2 (HER2) status
• Where cancer has spread
• The genetic characteristics of the cancer cells
• Treatment history and outcome
• Site-specific symptoms the patient is experiencing

Hormone Therapy - Aromatase Inhibition, Anti-estrogens & Ovarian Suppression

During the diagnosis stage, hormone receptor status of breast cancer is determined by analyzing a tissue biopsy. Hormone receptor-positive metastatic breast cancer grows via exposure to the primary female sex hormones, estrogen, and progesterone. These hormones are produced primarily in the ovaries. Although the mechanism of action may vary, drugs like tamoxifen, anastrozole, and goserelin inhibit the production or absorption of estrogen in various tissues and are therefore effective in treating these types of metastases.

Whether or not an aromatase inhibitor (AI) like anastrozole, selective estrogen receptor modulators (SERM) like tamoxifen, or a gonadotropin-releasing hormone agonist (GnRH agonist) like goserelin is to be used by your Oncologist, depends upon on your menopausal status and prior history of treatment.

Premenopause

Premenopause women almost always begin metastatic breast cancer treatment with therapies that suppress the production of estrogen within the ovaries via GnRH administration. Ovarian suppression via drug therapy is effective in premenopause women because the ovaries are still producing estrogen and progesterone. GnRH agonists elicit a negative feedback loop via the hypothalamic-pituitary-gonadal axis (HPG axis). In simpler terms, the natural cascade of hormones responsible for signaling the ovaries is disrupted, resulting in a decrease of estrogen production. In rarer cases, removal of the ovaries may also be an option.

Postmenopause

In postmenopausal women, the ovaries are no longer produce high levels of estrogen and progesterone, as they are already in a state of suppression. Treatment of metastatic breast cancer in postmenopausal patients may begin with the administration of aromatase inhibitors or SERMs.

Aromatase inhibitors, or AIs, work by shutting down the conversion of certain hormones (including progesterone, testosterone, and cholesterol) to estrogen via the aromatase enzyme found in skin, bone, ovarian, adrenal glands, and even brain tissues.

SERMs mediate estrogen actions in tissues throughout the body by binding to estrogen receptors within cells. Some SERMs like tamoxifen have mixed agonistic/antagonistic effects in different tissues; that is to say that some cells continue producing estrogen (agonist actions are exerted) while others stop (antagonist actions are exerted). Other SERMs such as fulvestrant have full antagonistic effects on all tissues, resulting in complete suppression of estrogen production.

The first choice in most postmenopausal women is usually an AI, however, in certain cases can also be oral tamoxifen.

Targeted Therapies

When breast cancer metastasizes, it can affect a wide variety of tissues and develop a multitude of different biological characteristics. Targeted therapies allow physicians the freedom to develop comprehensive lines of treatment based on the individual factors present in each patient’s cancer.

The following sections discuss various therapies that are effective in slowing the progression of metastatic breast cancer. If you have any questions or concerns regarding what’s right for you, don’t hesitate to contact us at ACTCHealth.com and request an appointment today.

Anti-HER2 Drugs

The treatment of HER2-positive metastases involves the administration of targeted antibodies such as trastuzumab or pertuzumab.

CDK4/6 Inhibitors

CDK4/6 inhibitors interrupt the function of cyclin-dependent kinase enzymes that signal cancer cells to enter their final growth stage and undergo division. CDK4/6 inhibitors are often used in conjunction with hormone therapy to treat hormone-receptive, HER2-negative metastatic breast cancer. They can sometimes be used by themselves.
Examples of CKD4/6 inhibitors include drugs such as Abemaciclib, Ribociclib, and Palbociclib.

mTOR Inhibitors

Mammalian target of rapamycin (mTOR) inhibitors works similarly to CDK4/6 inhibitors to interrupt the proliferation of cancer cells. They are used in combination with hormone therapy to more effectively control the spread of hormone receptor-positive, HER2-negative metastatic breast cancer.

Chemotherapy

When combined with anti-HER2 targeted therapy, chemotherapy may be effective at treating HER2-positive metastatic breast cancer regardless of hormone receptor status, although it is typically called in to treat hormone receptor-positive metastases only after hormone therapies have failed.