Complications

Complication
Timeframe
Likelihood
long term
medium

After 5 years of treatment with tamoxifen, relative risk of tamoxifen-related endometrial cancer is 2.5 compared with no treatment.[140] The risk of endometrial cancer is less with raloxifene than with tamoxifen.[128]

Endometrial cancer

variable
medium

Ductal carcinoma in situ (DCIS) is a potential precursor of invasive carcinoma and suggests that cancer will become invasive at that site.[1]​​ Lobular carcinoma in situ (LCIS) develops in breast lobule(s) and/or terminal ducts and is usually found incidentally. Whereas DCIS predicts an increased risk of invasive ductal carcinoma developing at the site of a biopsy demonstrating DCIS, LCIS implies increased risk of invasive ductal or lobular carcinoma developing in either breast.[2]​​ LCIS is not cancer but a pathologic description of a neoplastic proliferation of cells within lobules and/or terminal ducts, which is a risk factor for invasive breast cancer.​​[3] A finding of LCIS does not imply that cancer will form at the diagnostic site. Consequently, treatment for LCIS is less formalized than for DCIS.​

Primary invasive breast cancer

variable
medium

In one randomized trial, the relative risk of hospitalization or death from a pulmonary embolus after taking tamoxifen for 10 years compared with stopping after 5 years was 1.87 (95% CI 1.13 to 3.07, P=0.01), with a 0.2% risk of death in both groups.[141] In the shorter term, the thromboembolic effects of tamoxifen increase the risk of skin flap necrosis during breast reconstruction performed as a delayed procedure after mastectomy.[142]

Pulmonary embolism

variable
medium

The use of aromatase inhibitors in women with breast cancer is associated with a greater cardiovascular risk than tamoxifen.[143]

variable
medium

In patients receiving whole breast radiation therapy (WBRT), a small portion of the lung and ribs receive radiation, which can induce lung scarring and slightly increase the risk of rib fracture. Furthermore, the heart is incidentally exposed to small doses of radiation when treating left-sided breast cancers, which may increase the risk of ischemic heart disease.[115] Risk of ischemic heart disease may increase with increasing doses of radiation to the heart.[115]​ Newer techniques, such as hypofractionated and ultra-hypofractionated WBRT regimens and accelerated partial breast irradiation/partial breast irradiation (APBI/PBI), minimize the dose and, therefore, sequelae.[116]

APBI/PBI using external beam radiation therapy (EBRT) given once daily or on alternate days is associated with improved cosmesis and reduced acute and late toxicities compared with WBRT.[103][106]​​[113]​ Twice-daily EBRT regimens are associated with worse late toxicity and cosmesis.[101]​​[102]​​​

APBI/PBI using multicatheter brachytherapy has shown similar late toxicity outcomes to WBRT, with comparable or improved cosmesis.[101]​[104][107][114]​​

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