September 19, 2019
Article from January 2019, Summary by Cécile Bour, MD
Evaluation of the Incidence of Hematologic Malignant Neoplasms Among Breast Cancer Survivors in France
JAMA Network Open. 2019;2(1):e187147. doi:10.1001/jamanetworkopen.2018.7147
Marie Joelle Jabagi, PharmD, MPH; Norbert Vey, MD, PhD; Anthony Goncalves, MD, PhD; Thien Le Tri, MSc; Mahmoud Zureik, MD, PhD; Rosemary Dray-Spira, MD, PhD
About this study
This is a cohort study. All French women between the ages of 20 and 85 years who were diagnosed with breast cancer and did not die (referred to as "survivors"), between 2006 and 2015, were included and were followed up until the onset of hematological cancer, or until death, or until loss of follow-up, as the case may be. Comparisons were made with all French women in general population enrolled in general health insurance plan each year from 2007 to 2016. Data from the SNDS (containing data from the PMSI and the CepiDC) were analyzed.
The different types of hematological neoplasia considered were acute myeloid leukemia, myelodysplastic syndrome, myeloproliferative neoplasms, multiple myeloma, Hodgkin's lymphoma or non-Hodgkin's lymphoma, acute lymphoblastic leukemia, lymphocytic lymphoma. The incidence (number of new cases) of these different types was estimated and compared to the incidence in women in general population.
In this study of 439,704 French women, women with a diagnosis of breast cancer who had not died from it, had a statistically standardized higher incidence of acute myeloid leukemia and myelodysplastic syndrome compared to women in general population. There was a slight increase in the incidence of multiple myeloma and acute lymphoblastic leukemia.
French women participating in the study who had breast cancer in the last decade were 3X more likely to develop acute myeloid leukemia and five times more likely to develop myelodysplastic syndrome than women in general population. Several previous studies have linked these pathologies to chemotherapeutic agents, radiotherapy, and taxotere therapy (adjuvant treatment of breast cancer, see HAS 2015 advisory). (See studies )
It cannot be ignored that hematological risk of malignant neoplasm reaches peaks within specific time frames after breast cancer.
The annual incidence of acute myeloid leukemia in these patients from this study, increased during the first few years following diagnosis of breast cancer, with an early peak around year three and a subsequent peak around year eight. This finding is consistent with previous studies indicating the presence of 2 types of acute lymphocytic leukemia associated with treatment.
The authors suggest that the latency of onset may depend on the age of the patient at diagnosis, type of therapy and dosage regimen, and also on the limited time of follow-up in the study (even later cases may occur that have not been reported here).
The majority of secondary leukemias are of the myeloid type, but it is estimated that acute secondary lymphoblastic leukemias account for 10% to 12% of all secondary leukemias, with breast cancer being the most common cancer causing these secondary pathologies. In this study, there was a two-fold increase in the incidence of acute lymphocytic leukemia in breast cancer "survivors". Some studies showed that irradiation and chemotherapy were associated with pathogenesis , while other studies suggested that prior therapy plays a less important role in secondary acute lymphocytic leukemia than genetic predisposition .
A 50% increase in the incidence of multiple myeloma was observed in breast cancer survivors in this study. This slight increase has not been reported and needs to be further investigated, particularly the role of susceptibility due to heredity in BCRA1 and BCRA2 mutation carriers. 
This study reveals that acute myeloid leukemia, myelodysplastic syndrome and acute lymphoblastic leukemia are more common in treated women who do not die from breast cancer than in women in the general population; this is of concern and according to the authors, ongoing surveillance of hematological malignancies and further research into the underlying mechanisms of these diseases is needed.
This study is intended to better inform practicing oncologists; patients with a history of breast cancer should be informed of the increased risk of developing certain hematologic malignancies after their first cancer diagnosis.
Recent discovery of genetic signatures that guide treatment decisions in early stages of breast cancer could reduce the number of patients exposed to cytotoxic chemotherapy and its complications, including hematological cancers.
It is therefore necessary to continue monitoring trends in the occurrence of hematological cancers, especially as approaches to cancer treatment are evolving rapidly. Further research is also needed to evaluate treatment modality in cases of genetic predisposition to secondary malignancies.
Concerns about overdiagnosis are all the more justified because women, some of whom are at high risk and unaware of it , may be receiving radiation therapy that they would not have needed, and are being precipitated by screening for a disease they would not have had in its absence, with potential risks inherent in treatment, including secondary hematological diseases.
This has been shown in studies that suggest that risks of treatment may outweigh the expected benefit of screening. 
As our dotted poster on the home page of the site (bottom of the page, "poster") shows, the benefit/risk balance in screened women is far from being in favor of benefit, due to overdiagnosis, radiation-induced cancers, radiation-induced coronaritis, surgical and anesthetic accidents, post-treatment thromboembolism, and secondary hematopathies.
The Cancer Rose Collective regrets that these elements are not explicitly detailed in the information brochure given to women who are part of the new study on personalized screening, the MyPebs study. Overdiagnosis is minimized at rates that are currently obsolete, overtreatment, a tangible consequence resulting from overdiagnosis for women, is not stated, and consequences of treatment are not mentioned.
 Studies about relation between breast cancer treatment and Hematologic Malignant Neoplasms:
- SmithRE,BryantJ,DeCillisA,AndersonS;National Surgical Adjuvant Breast and Bowel Project Experience. Acute myeloid leukemia and myelodysplastic syndrome after doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: the National Surgical Adjuvant Breast and Bowel Project Experience. J Clin Oncol. 2003;21 (7):1195-1204. doi:1200/JCO.2003.03.114
- PragaC,BerghJ,BlissJ,etal.Risk of acute myeloid leukemia and myelodysplastic syndrome in trials of adjuvant epirubicin for early breast cancer: correlation with doses of epirubicin and cyclophosphamide. J Clin Oncol. 2005;23(18):4179-4191. doi:1200/JCO.2005.05.029
- BeadleG,BaadeP,FritschiL.Acute myeloid leukemia after breast cancer:a population-based comparison with hematological malignancies and other cancers. Ann Oncol. 2009;20(1):103-109. doi:1093/annonc/mdn530
- Le Deley M-C, Suzan F, Cutuli B, et al. Anthracyclines, mitoxantrone, radiotherapy, and granulocyte colony- stimulating factor: risk factors for leukemia and myelodysplastic syndrome after breast cancer. J Clin Oncol. 2007; 25(3):292-300. doi:1200/JCO.2006.05.9048
- Galper S, Gelman R, Recht A, et al. Second non breast malignancies after conservative surgery and radiation therapy for early-stage breast cancer. Int J Radiat Oncol Biol Phys. 2002;52(2):406-414. doi:1016/S0360-3016 (01)02661-X
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- CurtisRE,BoiceJDJr,StovallM,FlanneryJT,MoloneyWC.Leukemia risk following radiotherapy for breast cancer. J Clin Oncol. 1989;7(1):21-29. doi:1200/JCO.1918.104.22.168
- HsuW-L,PrestonDL,SodaM,etal.The incidence of leukemia,lymphoma and multiple myeloma among atomic bomb survivors: 1950-2001. Radiat Res. 2013;179(3):361-382. doi:1667/RR2892.1
- AndersenMK,ChristiansenDH,JensenBA,ErnstP,HaugeG,Pedersen-BjergaardJ.Therapy-related acute lymphoblastic leukaemia with MLL rearrangements following DNA topoisomerase II inhibitors, an increasing problem: report on two new cases and review of the literature since 1992. Br J Haematol. 2001;114(3):539-543. doi:1046/j.1365-2141.2001.03000.x
 GanzelC,DevlinS,DouerD,RoweJM,SteinEM,TallmanMS.Secondary acute lymphoblastic leukaemiais
constitutional and probably not related to prior therapy. Br J Haematol. 2015;170(1):50-55. doi:10.1111/bjh.13386
 StruewingJP,HartgeP,WacholderS,etal.The risk of cancer associated with specific mutations of BRCA1and
BRCA2 among Ashkenazi Jews. N Engl J Med. 1997;336(20):1401-1408. doi:10.1056/NEJM199705153362001
- CardosoF,van’tVeerLJ,BogaertsJ,etal;MINDACTInvestigators.70-Gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016;375(8):717-729. doi:1056/NEJMoa1602253
- SparanoJA,GrayRJ,MakowerDF,etal.Adjuvant chemotherapy guided by a21-gene expression assay in breast cancer. N Engl J Med. 2018;379(2):111-121. doi:1056/NEJMoa1804710