What is the risk of developing metastatic (secondary) cancer from a primary breast cancer?

From the Guidelines

Secondary cancer from breast primary is best managed with a multidisciplinary approach, considering systemic therapy, local treatment, and patient preferences, with the goal of controlling the disease, extending life, and maintaining quality of life. When considering treatment options for metastatic breast cancer, it is essential to take into account the cancer's hormone receptor status, HER2 status, previous treatments, extent of disease, and the patient's overall health 1. The choice of therapy should be made after consideration of these factors, and patients' preferences should always be taken into account, not only about treatment options but also methods of treatment administration (intravenous or oral) 1. Some key considerations in the management of metastatic breast cancer include:

• Systemic treatment options such as endocrine therapy, chemotherapy, and biological agents like trastuzumab, bevacizumab, and lapatinib 1
• The use of bisphosphonates or denosumab for the treatment of hypercalcemia and clinically evident bone metastases to palliate symptoms and decrease the risk of bone events 1
• Local treatments such as radiation therapy or surgery for specific symptoms or complications, including bone metastases, brain metastases, and painful or fungating soft tissue masses 1
• The potential benefit of removing the primary tumor in patients with metastatic disease, although prospective randomized trials addressing this question are currently ongoing 1 It is crucial to regularly monitor patients with imaging studies and tumor marker tests to assess treatment response and guide adjustments to the treatment plan as needed. Ultimately, the goal of treatment for secondary cancer from breast primary is to control the disease, extend life, and maintain quality of life, rather than to achieve a cure.

From the FDA Drug Label

Secondary acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) has been reported in patients treated with anthracyclines, including doxorubicin The rate of developing secondary AML or MDS has been estimated in an analysis of 8,563 patients with early breast cancer treated in 6 studies conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP), including NSABP B-15 Among 4,483 such patients who received conventional doses of AC, 11 cases of AML or MDS were identified, for an incidence of 0.32 cases per 1,000 patient years (95% Cl, 0.16 to 0. 57) and a cumulative incidence at 5 years of 0.21% (95% Cl, 0.11 to 0.41%). In another analysis of 1,474 patients with breast cancer who received adjuvant treatment with doxorubicin-containing regimens in clinical trials conducted at University of Texas M.D. Anderson Cancer Center, the incidence was estimated at 1. 5% at 10 years.

The risk of secondary cancer, specifically acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), in patients with breast primary treated with doxorubicin is estimated to be:

• 0.21% at 5 years in patients who received conventional doses of AC, based on an analysis of 4,483 patients 2
• 1.5% at 10 years in patients who received adjuvant treatment with doxorubicin-containing regimens, based on an analysis of 1,474 patients 2 Risk factors for secondary AML or MDS include:
• Higher cyclophosphamide dosages
• Radiotherapy
• Age 50 or older
• Pediatric patients are also at risk of developing secondary AML 2

From the Research

Secondary Cancer from Breast Primary

There are no direct research papers to assist in answering this question. However, the provided studies discuss various treatments and therapies for breast cancer, including:

• Adjuvant chemotherapy regimens such as doxorubicin plus cyclophosphamide 3
• Neoadjuvant chemotherapy with nab-paclitaxel, doxorubicin, and cyclophosphamide 4
• Neoadjuvant therapy with doxorubicin-cyclophosphamide followed by weekly paclitaxel 5
• Adjuvant dose-dense doxorubicin plus cyclophosphamide followed by dose-dense nab-paclitaxel 6
• Pegylated liposomal doxorubicin and cyclophosphamide as first-line therapy for patients with metastatic or recurrent breast cancer 7

Key Findings

• The combination of doxorubicin and cyclophosphamide is a standard adjuvant chemotherapy regimen 3
• Neoadjuvant chemotherapy with nab-paclitaxel, doxorubicin, and cyclophosphamide resulted in high clinical and pathologic responses, particularly in triple-negative breast cancer 4
• Neoadjuvant therapy with doxorubicin-cyclophosphamide followed by weekly paclitaxel can be safely administered in the "real-world" setting with high efficacy 5
• Adjuvant dose-dense doxorubicin plus cyclophosphamide followed by dose-dense nab-paclitaxel is feasible in women with early-stage breast cancer, with manageable adverse events 6
• Pegylated liposomal doxorubicin and cyclophosphamide as first-line therapy for patients with metastatic or recurrent breast cancer is active and well tolerated 7

Treatment Options

• Doxorubicin plus cyclophosphamide 3
• Nab-paclitaxel, doxorubicin, and cyclophosphamide 4
• Doxorubicin-cyclophosphamide followed by weekly paclitaxel 5
• Dose-dense doxorubicin plus cyclophosphamide followed by dose-dense nab-paclitaxel 6
• Pegylated liposomal doxorubicin and cyclophosphamide 7