A 72-Year-Old Woman With Back Pain and Hypercalcemia

Tarah Ballinger, MD; Kathy D. Miller, MD


July 27, 2016

A change in ER/PR or HER2 status can have implications for both prognosis and treatment. In general, survival decreases after recurrence, and overall survival decreases for patients with discordant receptor results between the primary tumor and the recurrent tumor. The poorest outcome is seen in patients who develop a triple-negative phenotype, those who lose ER positivity, or those who lose HER2 positivity.[4,5,7,10] This is probably due to inappropriate therapy choices and lack of effectiveness of targeted therapies.

Another important reason for repeat biopsy of recurrent disease is the possibility of a secondary cancer, as was the case for this patient. Secondary cancers are a significant cause of morbidity and mortality in cancer survivors, and patients should be monitored for their occurrence. Patients with breast cancer who have been previously treated with chemotherapy or radiation are at higher risk for numerous long-term treatment-related complications, including secondary cancers. One source of this increased risk comes from adjuvant radiation, use of which has dramatically increased after randomized trials showing similar outcomes for breast-conserving surgery followed by radiation, compared with total mastectomy.[11]

Prior large retrospective studies have found an increased risk for acute leukemia, sarcoma, and lung cancer in patients with breast cancer who received radiation therapy.[12,13] Chemotherapy also increases the risk for secondary cancers, particularly bone marrow neoplasms, such as acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Therapy-related AML/MDS accounts for approximately 20% of cases.

Two variants of this type of AML/MDS are noted. The first type results from topoisomerase II inhibitors (ie, anthracyclines, such as doxorubicin), with a lifetime risk of less than 1% and a latency period of 1-3 years after treatment; disease is characterized by a chromosome 11q23 translocation. The other results from DNA-alkylating agents (such as cyclophosphamide), with a lifetime incidence of 1%-5% and a latency period of 4-6 years; disease is characterized by deletions of chromosome 5 or 7. This is meaningful for patients with breast cancer, many of whom receive four cycles of both doxorubicin plus cyclophosphamide in the neoadjuvant or adjuvant setting.[14]

A large prospective study of 20,000 patients with early-stage breast cancer found a 10-year risk of 0.5% for the development of AML or MDS.[15] These therapy-related leukemias are very refractory to treatment and have a high mortality rate. For the patient in this case, who had an intermediate probability of recurrent disease and therefore derives an uncertain benefit from adjuvant chemotherapy, this was an important risk to take into account.


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