Risk of Hematologic Malignant Neoplasms after Postoperative Treatment of Breast Cancer.

Marie Joelle Jabagi,Thien Le Tri,Norbert Vey,Rosemary Dray-Spira,Anthony Goncalves,Mahmoud Zureik

doi:10.3390/cancers11101463

Abstract

An indirect consequence of the improved long-term survival seen in patients with breast cancer (BC) is the increased risk of hematologic malignant neoplasms (HM). This study aimed to analyze the role of postoperative treatment for BC in the development of subsequent HM. Using the French National Health Data System, we examined the HM risks in patients diagnosed with an incident primary breast cancer between 2007 and 2015, who underwent surgery as first-line treatment for BC. Main outcomes were acute myeloid leukemia (AML), Myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), multiple myeloma (MM), Hodgkin’s lymphoma or non-Hodgkin’s lymphoma (HL/NHL), and acute lymphoblastic leukemia or lymphocytic lymphoma (ALL/LL). Analyses were censored at HM occurrence, death, loss to follow up, or December 2017. The risk of each type of HM was compared according to the initial postoperative treatment of breast cancer. Of a total of 324,056 BC survivors, 15.5% underwent surgery only, 46.7% received radiotherapy after surgery, 4.3% received chemotherapy after surgery, and 33.5% received all three modalities. Overall, 2236 cases of hematologic malignancies occurred. Compared to the surgery alone group, AML was significantly increased after surgery plus radiation (aHR, 1.5; 95% CI, 1.0–2.1), surgery plus chemotherapy (aHR, 2.1; 95% CI, 1.2–3.6) and all modalities (aHR, 3.3; 95% CI, 2.3–4.7). MDS was significantly increased after surgery plus chemotherapy (aHR, 1.7; 95% CI, 1.1–2.5) or after all modalities (aHR, 1.4; 95% CI, 1.1–1.8). HL/NHL were significantly increased only in the radiotherapy and surgery group (aHR, 1.3; 95% CI, 1.0–1.6). A nonsignificant increase of ALL/LL (aHR, 1.8; 95% CI, 0.6–3.5) was noted after chemotherapy and with all three modalities (aHR, 1.4; 95% CI, 0.7–2.8). Our population based study revealed increased risks of various HM associated with postoperative BC treatment. The added benefit of chemotherapy and radiation therapy should take into consideration these long-term complications.

Highlights

Detection and improved therapeutic options including, endocrine therapy, cytotoxic chemotherapy, targeted therapies, and radiation therapy have led to improved survival in breast cancerCancers 2019, 11, 1463; doi:10.3390/cancers11101463 www.mdpi.com/journal/cancers (BC), the most common and often curable malignant solid tumor in women
There was a significant increase in acute myeloid leukemia (AML) and Hodgkin’s lymphoma or non-Hodgkin’s lymphoma (HL/NHL) risk if radiotherapy was added to surgery and a marked significant increase of AML, and to a lesser extent of Myelodysplastic syndrome (MDS) and acute lymphoblastic leukemia or lymphocytic lymphoma (ALL/LL), if chemotherapy with or without radiation therapy was added to surgery
We found a 1.7-fold increased risk of ALL/LL after chemotherapy while exposure to radiation therapy did not seem to be associated with an increased risk

Summary

Introduction

Detection and improved therapeutic options including, endocrine therapy, cytotoxic chemotherapy, targeted therapies, and radiation therapy have led to improved survival in breast cancerCancers 2019, 11, 1463; doi:10.3390/cancers11101463 www.mdpi.com/journal/cancers (BC), the most common and often curable malignant solid tumor in women. Detection and improved therapeutic options including, endocrine therapy, cytotoxic chemotherapy, targeted therapies, and radiation therapy have led to improved survival in breast cancer. A major concern, is the rising rates of secondary malignancies in this steadily growing population of cancer survivors. Myeloid neoplasms such as acute myeloid leukemia (AML) and Myelodysplastic syndrome (MDS). Breast cancer has ranked among the most common malignant solid tumors at risk for their development [6,7]. The exact magnitude of the risk of these two secondary hematological malignancies after a postoperative treatment for breast cancer in the current context is not clear. Previous studies based on hospital series have reported treatment-related lymphocytic leukemia and lymphomas [8,9,10,11,12]

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