Lymphedema Is 'Multimodal Insult,' Say Breast Surgeons

Nick Mulcahy

April 28, 2017

The risk for lymphedema in patients with breast cancer is not solely tied to surgery but is also associated with multiple other factors, including radiation therapy and chemotherapy, new research confirms.

"It’s a multimodal insult to the axilla — the surgery has an impact, the radiation has an impact, and the chemotherapy has an impact," summarized senior author Judy Boughey, MD, a surgeon at the Mayo Clinic in Rochester, Minnesota.  

Surgeons can expect to hear otherwise from their patients, she suggested.

Most breast cancer patients have a "significant" fear of the chronic arm swelling and they "mostly" associate it with axillary lymph node dissection, Dr Boughey said during a presscast from the American Society of Breast Surgeons annual meeting in Las Vegas.

Overall, clinicians are also largely unaware of the multiple risk factors, especially chemotherapy, said another expert.

"We see this additive effect of surgery, radiation, and chemotherapy — that's not something that most clinicians recognize," said Sarah McLaughlin, MD, a surgeon at the Mayo Clinic in Jacksonville, Florida, who was not involved with the study.

She also "would bet" that most physicians don’t see chemotherapy as a risk.

Taxane-based chemotherapy, in particular, is associated with increased risk but has not been well studied or documented, added Dr McLaughlin, who is hosting a panel discussion on lymphedema at the meeting. 

In multidisciplinary settings, patients will talk to their surgeon and radiation oncologist about lymphedema, but not their medical oncologist, said Dr Boughey.

In the new study, Dr Boughey and Mayo Clinic colleagues reviewed the charts of 1794 women with stage 0 to III breast cancer who were treated between 1990 and 2010 in Olmsted County, Minnesota. Median follow-up was about 10 years.

About 40% of the women had axillary lymph node dissection (ALND) and about 40% had the less invasive sentinel lymph node biopsy (SLNB).

Within 5 years, 5.3% of SLNB and 15.9% of ALND patients developed lymphedema (P < .001). The form of breast surgery (mastectomy or lumpectomy) did not matter. However, notably, all patients who developed lymphedema within 5 years received some form of axillary surgery. In other words, it was the axillary surgery that was a necessary part of the risk.

However, 57% of the patients received radiation therapy and 28% received chemotherapy.

So the investigators looked at the impact of these two modalities on the risk for lymphedema.

Notably, adjuvant radiation therapy did not affect lymphedema rates in SLNB-only patients (6.3% with vs 3.6% without; P = .15), but it did in ALND patients (22.2% vs 7.8%, respectively; P < .001).

In multivariable analysis (among patients with any axillary surgery), adjuvant radiation therapy was significantly associated with lymphedema, with an adjusted hazard ratio (HR) of 2.7 (95% confidence interval [CI], 1.9 - 3.9).

Chemotherapy was also significantly associated with lymphedema (HR, 1.8, 95% CI, 1.2 - 2.8), as was advanced stage disease (stage III [HR, 2.2; 95% CI, 1.2 - 3.7] vs stage 0/I).

Overweight was also a risk factor for lymphedema. Patients with a body mass index of 35 or greater or 25 to 34.99 had higher rates of the chronic arm swelling than those with a body mass index less than 25 (P < .01).

Finally, ALND was significantly associated with lymphedema, with an HR of 2.0 (95% CI, 1.3 - 3.1).

The cumulative nature of the lymphedema risk with the addition of each major modality was well illustrated among the patients who underwent ALND.


Treatment Combo

Patients (n)

5-Year Risk (%)

10-Year Risk (%)

ALND only
















CT = chemotherapy; RT = radiation therapy.


In general, rates of lymphedema in the study were highest in patients with advanced stage disease who were treated with all three major modalities, said Dr Boughey.

She also highlighted the way in which inclusion of taxanes in a chemotherapy regimen drove up the rate of lymphedema.



Patients (n)

5-Year Incidence (%)




Other agents



AC without taxane



Taxane without AC



AC + taxane



A = doxorubicin (also known as Adriamycin ); C = cyclophosphamide.


There is increasing scrutiny of the role of chemotherapy, especially taxanes, in the development of lymphedema, Dr McLaughlin said.

Dr Boughey and Dr McLaughlin have disclosed no relevant financial relationships.

American Society of Breast Surgeons 18th Annual Meeting. To be presented April 29, 2017.

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