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Debunking the Myth of Lymphedema Risk
Axillary Surgery Only One Factor
Abstract: Breast cancer related lymphedema risk is related to multidisciplinary treatment and not surgery alone—results from a large cohort study.
Las Vegas, April 27, 2017--Breast cancer-related lymphedema, chronic swelling of the arm and chest area, is strongly associated with multi-modality therapies and not axillary node surgery alone as widely believed, according to a new study presented this week at the Annual Meeting of the American Society of Breast Surgeons.
The study found that chemotherapy, more advanced disease and greater than normal body weight significantly increased the risk of lymphedema for patients who had surgery of lymph nodes under their arms to assess the spread of cancer.Radiation therapy also strongly correlated with lymphedema for patients undergoing axillary node dissection (ALND), the more invasive form of axillary surgery.
“Lymphedema rate was significantly lower amongpatients undergoing axillary surgery without these additional risk factors,” says study co-author Judy Boughey, M.D., FACS, professor of surgery and research chair, department of surgery at Mayo Clinic. “We must recognize that today, breast cancer is no longer a disease treated primarily through surgery, and many therapies impact the risk of this chronic condition. Risk factors appeared to be cumulative, affecting women in a step-like fashion.”
According to Dr. Boughey, most breast cancer patients are extremely concerned about developing lymphedema, and this study provides important new information furthering an understanding of the condition. “It has long been widely assumed that axillary surgery is the dominant factor affecting lymphedema development,” she says.
Dr. Boughey notes that axillary surgery for lymph node staging can involve sentinel lymph node biopsy (SLNB), which involves removal of an average of two or three lymph nodes, or ALND, usually involving removal of between 10 and 30 nodes. ALND was not associated with a higher lymphedema rate than SLNB unless chemotherapy or radiation therapy was involved.
The new study included 1794 women with stage 0 to 3 breast cancer between 1990 and 2010 drawn from a large regional database. Of these patients, 59% underwent breast-conserving lumpectomy, 28% unilateral mastectomy and 13% bilateral mastectomy. The type of breast surgery was not associated with lymphedema development.
Forty-four percent of patients were treated with ALND with an average of 16 nodes removed, while 40% had SLNB with an average of 3 nodes removed. Within five years, 5.3% of SLNB and 15.9% of ALND patients developed lymphedema. In the study, all patientswho developed lymphedema within five years had undergone some form of axillary surgery.
The study found that lymphedema was associated with stage 2 and 3 disease because patients typically were treated with radiation and/or chemotherapy. Lymphedema risk also increased with higher body mass index (BMI) considered overweight and additionally for women considered obese.
“Clearly, for a realistic perspective on lymphedema risk, women should talk not only to their surgeons but also to their oncologists and radiation oncologists and take into account the full multidisciplinary treatment that they are undertaking,” comments Dr. Boughey.
She also notes that treatment options for lymphedema have improved during the past decade. “Patients with a high lymphedema risk profile should be carefully followed so that any necessary interventions can begin early,” she advises.
Expert Commentary:
“This study stresses the importance of preoperative patient counseling regarding lymphedema,” notes Deanna Attai, M.D., assistant clinical professor of surgery at the David Geffen School of Medicine at UCLA and ASBrS immediate past-president. “Lymphedema can have a significant impact on long term quality of life, and patients will benefit from a multidisciplinary approach to education on this topic.”
Abstract updated as of April 17, 2017
Presenter: Judy C. Boughey, M.D.
Institution:Mayo Clinic
Objective: Breast-cancer related lymphedema (BCRL) is a significant complication in women undergoing treatment. In this study, we aim to assess BCRL incidence and risk factors over up to 22 years follow up among a large population-based cohort.
Methods: We utilized the Olmsted County Rochester Epidemiology Project Breast Cancer Cohort, a population-based sample of all incident breast cancer cases diagnosed in Olmsted County, MN residents in 1990-2010. Charts were electronically and manually reviewed to ascertain definite or probable breast-cancer related lymphedema (BCRL). Time to BCRL was calculated from definitive breast surgery to date of diagnosis of BCRL. Variables collected included type of breast and axillary surgery, receipt of radiation and chemotherapy, cancer stage, and baseline BMI. The cumulative incidence estimator was used to estimate the rate of BCRL diagnosis while accounting for the competing risk of death; competing risks regression was used for multivariable analysis assessing risk factors for BCRL, which are reported with hazard ratios (HRs) and 95% confidence intervals (CIs).
Results: A total of 1794 patients with stage 0-3 breast cancer with a median of 10 years follow-up were included. Median age at cancer diagnosis was 60 years; 44% were overweight or obese at index. Stage distribution was 17% stage 0, 47% stage I, 28% stage II, and 7% stage III. A majority (58.5%) underwent lumpectomy, 28% unilateral mastectomy, and 13% bilateral mastectomy. Most patients underwent axillary staging surgery (44% axillary dissection (ALND), 40% sentinel lymph node biopsy (SLNB), 16% no axillary surgery) and 57% received radiation (RT). The median number of lymph nodes examined was 3 for SLNB only and 16 in ALND. The cumulative incidence of BCRL diagnosis within 5 years was 9.1% (95% CI: 7.8-10.5%). Overall mastectomy vs lumpectomy was not associated with higher rates of BCRL (p=0.42) among patients with any axillary surgery. All patients with BCRL within 5 years had undergone axillary surgery. The 5-year incidence of BCRL was 5.3% in SLNB only and 15.9% in ALND patients (p < 0.001). Adjuvant RT did not impact BCRL rates in SLNB only patients (6.3% with RT vs 3.6% without, p=0.15), however it did in ALND patients (22.2% vs 7.8%, p < 0.001). In patients treated with surgery only (no radiation and no chemotherapy) BCRL rates were not different between ALND versus SLNB (p=0.36). In multivariable analysis among patients with any axillary surgery, ALND and adjuvant RT remained significantly associated with BCRL with adjusted HRs of 2.0 (95% CI: 1.3-3.1) for adjuvant RT and 2.7 (95% CI: 1.9-3.9) for ALND vs SLNB only. Chemotherapy was also significantly associated with BCRL (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 disease]. Patients with BMI≥35 (HR 1.9, 95% CI: 1.0-3.3) or BMI 25-34.99 (HR 1.5, 95% CI: 1.1-2.0) had higher rates of BCRL than those with BMI < 25, p < 0.01.
Conclusions: BCRL is a sequelae of multimodal breast cancer treatment that affects some breast cancer survivors. The risk of lymphedema was multifactorial and not impacted by axillary surgery alone. BCRL rates were higher in patients receiving chemotherapy, radiation, ALND, more advanced stage of disease, and higher BMI. Adjuvant RT carried a higher risk of lymphedema development in patients undergoing ALND but not SLNB.
Table 1. Cumulative incidence of BCRL diagnosis by patient and clinical factors among breast cancer patients undergoing axillary staging surgery (n=1512)
N / 2-year cumulative incidence / 5-year cumulative incidence / Univariate p-valueBaseline BMI / 0.02
<25 / 845 / 5.7% / 8.0%
25-29.99 / 399 / 11.1% / 14.4%
30-34.99 / 187 / 10.8% / 13.0%
≥35 / 76 / 15.8% / 17.1%
Stage / <0.001
0/I / 890 / 2.9% / 5.2%
II / 496 / 11.8% / 14.1%
III / 126 / 32.0% / 37.8%
Surgery / <0.001
BCS+SLNB / 450 / 5.4% / 6.0%
BCS+ALND / 357 / 9.6% / 14.7%
Mastectomy+SLNB / 276 / 2.9% / 4.0%
Mastectomy+ALND / 429 / 13.6% / 17.0%
Radiation Therapy / <0.001
No / 621 / 4.2% / 5.9%
Yes / 891 / 11.0% / 14.2%
Chemotherapy / <0.001
No / 998 / 4.0% / 6.0%
Yes / 514 / 16.5% / 20.3%
Treatment combination / <0.001
SLNB only / 220 / 2.7% / 4.1%
SLNB+RT / 328 / 4.9% / 5.2%
SLNB+CT / 61 / 1.7% / 1.7%
SLNB+RT+CT / 117 / 7.8% / 9.6%
ALND only / 233 / 1.7% / 3.5%
ALND+RT / 217 / 6.5% / 11.6%
ALND+CT / 107 / 14.2% / 17.2%
ALND+RT+CT / 229 / 25.9% / 32.3%
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