Roles of radiotherapy and chemotherapy in the development of contralateral breast cancer.
OBJECTIVE
Few studies have examined whether modern radiotherapy and chemotherapy affect the risk of contralateral breast cancer (CBC), and results are inconclusive.


METHODS
We assessed long-term risk of CBC in a predominantly young breast cancer (BC) population (n = 7,221), focusing on the effects of radiation dose, chemotherapy, and family history of BC. Risk of CBC was evaluated using Cox proportional hazards regression models.


RESULTS
Radiotherapy-associated risk of CBC increased with decreasing age at first treatment (age < 35 years, hazard ratio [HR] = 1.78; 95% CI, 0.85 to 3.72; age > 45 years, HR = 1.09; 95% CI, 0.82 to 1.45). Postmastectomy radiotherapy using direct electron fields led to a significantly lower radiation exposure to the contralateral breast than postlumpectomy radiotherapy using tangential fields. Women treated before age 45 years with postlumpectomy radiotherapy experienced 1.5-fold increased risk of CBC compared with those who had postmastectomy radiotherapy. The joint effects of postlumpectomy radiotherapy and strong family history for BC on risk of CBC were greater than expected when individual risks were summed (HR = 3.52; 95% CI, 2.07 to 6.02; P(departure from additivity) = .043). Treatment with adjuvant chemotherapy (cyclophosphamide, methotrexate, and fluorouracil) was associated with a nonsignificantly decreased risk of CBC in the first 5 years of follow-up but did not reduce CBC risk in subsequent years.


CONCLUSIONS
Young patients with BC irradiated with breast tangentials experience increased risk of CBC, especially in those with a positive family history of BC. This finding should be taken into account when advising breast radiation with tangential fields to young patients with BC. Adjuvant chemotherapy seemed to reduce the risk of CBC during the first 5 years after treatment only.
Department of Epidemiology, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
Maartje J
MJ
Hooning
Berthe M P
BM
Aleman
Michael
M
Hauptmann
Margreet H A
MH
Baaijens
Jan G M
JG
Klijn
Ruth
R
Noyon
Marilyn
M
Stovall
Flora E
FE
van Leeuwen
D000328:Adult; D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000175:diagnosis / Q000209:etiology; D016016:Proportional Hazards Models; D011878:Radiotherapy / Q000009:adverse effects*; D012306:Risk; D016896:Treatment Outcome
D000970:Antineoplastic Agents