The Risk of Breast Cancer Related Lymphedema Over Time
By Joachim Zuther, on September 8th, 2012
I am very grateful to Carol Doeringer, lymphedema patient
and advocate, who submitted this interesting and very insightful contribution
on the risk factors contributing to breast cancer related lymphedema. The
material is excerpted from a self-study course Carol has developed with the
support of friends and experts in the lymphedema and nursing communities. The
course is called Breast Cancer-Related Lymphedema: The Nurse’s Role in Care and
Prevention, the program will soon be available at no charge to any interested
nurse. Those interested can learn more by visiting the Lymphedema Speaks website
The Risk of Breast Cancer Related Lymphedema Over Time
Most women developing breast cancer related lymphedema (BCRL) will do so
within three years after breast cancer diagnosis. Survivors not developing
near-term BCRL retain a small lifetime risk. Norman et al (2009) found the
five-year cumulative incidence of BCRL was 42%. Of the affected women, 80%
developed lymphedema within two years and 89% within three years (1). Petrek et
al (2001) followed 263 patients after mastectomy and complete axillary
dissection. At 20 years after treatment, 49% reported lymphedema. Of those, 77%
noted onset within three years after surgery, and the remaining women developed
arm swelling at a rate of almost 1% per year (2).
Breast cancer treatments and BCRL risk
BCRL risk factors seem to be additive: A woman with breast conserving surgery
and no other treatment has less BCRL risk than a woman receiving breast
conserving surgery with axillary node dissection and radiation. Increasing the
number of nodes removed also increases BCRL risk (Paskett et al)(3). Sentinel
node biopsy, which removes one to seven nodes, brings a lower risk than
axillary node dissection, when 25 or more nodes might be removed. Shah and
Vicini (2011) summarized incidence ranges with various treatments, in their
BCRL-study review: (4)
Breast Cancer Treatment
Incidence Range
Lumpectomy alone
0-3%
Lumpectomy with SLN and breast
RT
3-23%
Lumpectomy with ALND and breast
RT
1-61%
Lumpectomy with regional nodal
RT
9-65%
Mastectomy with SLN, no RT
3-23%
Mastectomy with ALND, no RT
30-47%
Mastectomy with regional nodal
RT
58-65%
ALND with axillary RT
32%
ALND = axillary node dissection SLN=sentinel node RT=radiation
therapy
Most BCRL studies focus on arm lymphedema, which is readily measured once
past Stage 0, or subclinical BCRL. However, many breast cancer patients develop
lymphedema of the breast or trunk, with or without arm lymphedema. One
year after surgery, Ronka et al (2004) found breast edema identified by
clinical examination in 48% of patients with axillary clearance/ positive
nodes; in 35% with axillary clearance/ negative nodes; and in 23% with sentinel
node biopsy. Using ultrasound, they found subcutaneous breast edema in 69-70%
of the axillary clearance node patients and 28% of the sentinel node biopsy
patients (5). Sentinel node biopsy reduces arm lymphedema risk compared to
axillary clearance, but it poses a significant risk for breast lymphedema.
Additional cancer and related factors that influence BCRL
risk
Additional factors include cancer stage at diagnosis, chemotherapy, seroma,
and cording. Kwan et al (2010) found both advanced stage breast cancer and
chemotherapy to be associated with increased BCRL risk (6). Fu et al (2011)
found that patients with seroma requiring needle aspiration had 7.78 and 10.64
times the odds of developing arm swelling and chest/breast swelling,
respectively, compared to patients without symptomatic seroma (7). Cording (axillary web syndrome) is the appearance of
painful cord-like structures below the skin in an affected arm.
Key points
Personal factors that influence BCRL risk
Many women with multiple risk factors will never develop lymphedema, and some
women with very low suggested BCRL risk (such as mastectomy only) develop the
condition despite their seemingly favorable odds.
Why does one woman with statistically low BCRL risk develop lymphedema, and
another woman with multiple treatment-risk factors does not? A partial answer
may lie in two personal risk factors. Obesity at time of diagnosis is known to
be a significant risk factor for BCRL. In addition, recent research suggests
there may be a genetic predisposition to the condition.
Obesity is a known risk for developing BCRL. One
study that followed 138 breast cancer patients for 30 months found that those
with body mass indices of 30 or higher at the time of diagnosis were 3.6 times
more likely to develop lymphedema. The study found that weight gain after the
breast cancer diagnosis was not related to BCRL incidence (8). Of course,
asking a patient to engage in significant weight loss efforts at the time of
breast cancer treatment is not a realistic short-term means to reduce her BCRL
risks. Even so, knowing that her body weight adds to her BCRL risk may help
ensure that a breast cancer patient thinks of lymphedema and discusses early,
pre-clinical symptoms with her doctor instead of dismissing them as not
important.
Genetics likely also play a role in who develops and who
avoids BCRL. Lymphedema after breast cancer treatment is considered
secondary lymphedema, i.e. caused by damage or disruption to the
lymphatic system. Primarylymphedema is caused by abnormal
development of the lymphatic system, a rare genetic condition whose symptoms
may occur at birth or later in life. Lymphedema clinicians have long
hypothesized that some breast cancer survivors may have more robust lymphatic
transport capacity than others, so that women born with a ‘four-lane highway’
versus a ‘two-lane highway’ will be less susceptible to BCRL after damage to
their lymphatic nodes and/or vessels.
Recent studies may well support that hypothesis, identifying genetic
mutations in some women with BCRL. For example, Finegold et al (2012) (9)
studied 188 women diagnosed with breast cancer and sequenced candidate
lymphedema genes for mutation. Mutations were identified in individuals having
secondary lymphedema following breast cancer treatment but not in breast cancer
controls or women without breast cancer. The authors conclude that their
findings ‘challenge the view that secondary lymphedema is solely due to
mechanical trauma and support the hypothesis that genetic susceptibility is an
important risk factor for secondary lymphedema.’
Key points
Join Lymphedema Guru, a Facebook page solely
dedicated to inform about all things related to lymphedema – news, support
groups, treatment centers, and much more
1. Norman SA, Localio AR, Kallan MJ, Weber AL, Torpey HA,
Potashnik SL, Miller LT, Fox KR, DeMichele A, Solin LJ. (2010) Risk factors for
lymphedema after breast cancer treatment. Cancer Epidemiology, Biomarkers
& Prevention, 19(11):2734-46.
2. Petrek JA, Senie RT, Peters M, Rosen PP. (2001) Lymphedema in a
cohort of breast carcinoma survivors 20 years after diagnosis. Cancer,
92(6):1368-1377.
3. Paskett ED, Naughton MJ, McCoy TP, Case LD, Abbott JM. (2007)
The epidemiology of arm and hand swelling in premenopausal breast cancer
survivors. Cancer Epidemiology, Biomarkers & Prevention, 16(4):
775-782.
4. Shah C, Vicini FA (2011) Breast cancer-related arm lymphedema: Incidence
rates, diagnostic techniques, optimal management and risk reduction strategies.
International Journal of Radiation
Oncology·Biology·Physics,81(4):
907-914.
5. Rönkä RH, Pamilo MS, von Smitten KA, Leidenius MH. (2004)
Breast lymphedema after breast conserving treatment. Acta Oncologica.
43(6):551-7.
6. Kwan
ML, Darbinian J, Schmitz KH, Citron R, Partee P, Kutner SE, Hushi LH. (2010)
Risk factors of lymphedema in a prospective breast cancer survivorship study:
the Pathways Study, Archives of Surgery, 145(11):1055:1063.
7. Fu
MR, Guth AA, Cleland CM, Lima ED, Kayal M, Haber J, Gallup L, Axelrod D. (2011)
The effects of symptomatic seroma on lymphedema symptoms following breast
cancer treatment. Lymphology, 44(3):134-43.
8. Ridner SH, Dietrich MS, Stewart BR, et al. (2011) Body mass index
and breast cancer treatment-related lymphedema. Supportive Care in
Cancer 19 (6): 853-7.
9. Finegold D, Baty C, Knickelbein K. (2012) Connexin 47 mutations increase
risk for secondary lymphedema following breast cancer treatment. Clinical
Cancer Research, 18:2382-2390.
http://www.lymphedemablog.com/2012/09/08/the-risk-of-breast-cancer-related-lymphedema-over-time/
By Joachim Zuther, on September 8th, 2012
I am very grateful to Carol Doeringer, lymphedema patient
and advocate, who submitted this interesting and very insightful contribution
on the risk factors contributing to breast cancer related lymphedema. The
material is excerpted from a self-study course Carol has developed with the
support of friends and experts in the lymphedema and nursing communities. The
course is called Breast Cancer-Related Lymphedema: The Nurse’s Role in Care and
Prevention, the program will soon be available at no charge to any interested
nurse. Those interested can learn more by visiting the Lymphedema Speaks website
The Risk of Breast Cancer Related Lymphedema Over Time
Most women developing breast cancer related lymphedema (BCRL) will do so
within three years after breast cancer diagnosis. Survivors not developing
near-term BCRL retain a small lifetime risk. Norman et al (2009) found the
five-year cumulative incidence of BCRL was 42%. Of the affected women, 80%
developed lymphedema within two years and 89% within three years (1). Petrek et
al (2001) followed 263 patients after mastectomy and complete axillary
dissection. At 20 years after treatment, 49% reported lymphedema. Of those, 77%
noted onset within three years after surgery, and the remaining women developed
arm swelling at a rate of almost 1% per year (2).
Breast cancer treatments and BCRL risk
BCRL risk factors seem to be additive: A woman with breast conserving surgery
and no other treatment has less BCRL risk than a woman receiving breast
conserving surgery with axillary node dissection and radiation. Increasing the
number of nodes removed also increases BCRL risk (Paskett et al)(3). Sentinel
node biopsy, which removes one to seven nodes, brings a lower risk than
axillary node dissection, when 25 or more nodes might be removed. Shah and
Vicini (2011) summarized incidence ranges with various treatments, in their
BCRL-study review: (4)
Breast Cancer Treatment
Incidence Range
Lumpectomy alone
0-3%
Lumpectomy with SLN and breast
RT
3-23%
Lumpectomy with ALND and breast
RT
1-61%
Lumpectomy with regional nodal
RT
9-65%
Mastectomy with SLN, no RT
3-23%
Mastectomy with ALND, no RT
30-47%
Mastectomy with regional nodal
RT
58-65%
ALND with axillary RT
32%
ALND = axillary node dissection SLN=sentinel node RT=radiation
therapy
Most BCRL studies focus on arm lymphedema, which is readily measured once
past Stage 0, or subclinical BCRL. However, many breast cancer patients develop
lymphedema of the breast or trunk, with or without arm lymphedema. One
year after surgery, Ronka et al (2004) found breast edema identified by
clinical examination in 48% of patients with axillary clearance/ positive
nodes; in 35% with axillary clearance/ negative nodes; and in 23% with sentinel
node biopsy. Using ultrasound, they found subcutaneous breast edema in 69-70%
of the axillary clearance node patients and 28% of the sentinel node biopsy
patients (5). Sentinel node biopsy reduces arm lymphedema risk compared to
axillary clearance, but it poses a significant risk for breast lymphedema.
Additional cancer and related factors that influence BCRL
risk
Additional factors include cancer stage at diagnosis, chemotherapy, seroma,
and cording. Kwan et al (2010) found both advanced stage breast cancer and
chemotherapy to be associated with increased BCRL risk (6). Fu et al (2011)
found that patients with seroma requiring needle aspiration had 7.78 and 10.64
times the odds of developing arm swelling and chest/breast swelling,
respectively, compared to patients without symptomatic seroma (7). Cording (axillary web syndrome) is the appearance of
painful cord-like structures below the skin in an affected arm.
Key points
- 42-49% of breast cancer patients develop arm lymphedema within three years,
but BCRL is a lifetime risk.
- Node removal, radiation, surgery, chemotherapy, seroma and cording are
important, additive risk factors.
- Breast /trunk lymphedema is very common, but difficult to measure.
Ultrasound has detected subcutaneous breast edema in up to 70% of breast cancer
patients a year after surgery.
- Sentinel node biopsy reduces but does not eliminate arm lymphedema risk, and
it poses a significant risk for breast lymphedema.
Personal factors that influence BCRL risk
Many women with multiple risk factors will never develop lymphedema, and some
women with very low suggested BCRL risk (such as mastectomy only) develop the
condition despite their seemingly favorable odds.
Why does one woman with statistically low BCRL risk develop lymphedema, and
another woman with multiple treatment-risk factors does not? A partial answer
may lie in two personal risk factors. Obesity at time of diagnosis is known to
be a significant risk factor for BCRL. In addition, recent research suggests
there may be a genetic predisposition to the condition.
Obesity is a known risk for developing BCRL. One
study that followed 138 breast cancer patients for 30 months found that those
with body mass indices of 30 or higher at the time of diagnosis were 3.6 times
more likely to develop lymphedema. The study found that weight gain after the
breast cancer diagnosis was not related to BCRL incidence (8). Of course,
asking a patient to engage in significant weight loss efforts at the time of
breast cancer treatment is not a realistic short-term means to reduce her BCRL
risks. Even so, knowing that her body weight adds to her BCRL risk may help
ensure that a breast cancer patient thinks of lymphedema and discusses early,
pre-clinical symptoms with her doctor instead of dismissing them as not
important.
Genetics likely also play a role in who develops and who
avoids BCRL. Lymphedema after breast cancer treatment is considered
secondary lymphedema, i.e. caused by damage or disruption to the
lymphatic system. Primarylymphedema is caused by abnormal
development of the lymphatic system, a rare genetic condition whose symptoms
may occur at birth or later in life. Lymphedema clinicians have long
hypothesized that some breast cancer survivors may have more robust lymphatic
transport capacity than others, so that women born with a ‘four-lane highway’
versus a ‘two-lane highway’ will be less susceptible to BCRL after damage to
their lymphatic nodes and/or vessels.
Recent studies may well support that hypothesis, identifying genetic
mutations in some women with BCRL. For example, Finegold et al (2012) (9)
studied 188 women diagnosed with breast cancer and sequenced candidate
lymphedema genes for mutation. Mutations were identified in individuals having
secondary lymphedema following breast cancer treatment but not in breast cancer
controls or women without breast cancer. The authors conclude that their
findings ‘challenge the view that secondary lymphedema is solely due to
mechanical trauma and support the hypothesis that genetic susceptibility is an
important risk factor for secondary lymphedema.’
Key points
- Obesity at the time of breast cancer diagnosis is a known important risk
factor for developing BCRL.
- Genetics likely play a role in determining who will develop BCRL.
Join Lymphedema Guru, a Facebook page solely
dedicated to inform about all things related to lymphedema – news, support
groups, treatment centers, and much more
1. Norman SA, Localio AR, Kallan MJ, Weber AL, Torpey HA,
Potashnik SL, Miller LT, Fox KR, DeMichele A, Solin LJ. (2010) Risk factors for
lymphedema after breast cancer treatment. Cancer Epidemiology, Biomarkers
& Prevention, 19(11):2734-46.
2. Petrek JA, Senie RT, Peters M, Rosen PP. (2001) Lymphedema in a
cohort of breast carcinoma survivors 20 years after diagnosis. Cancer,
92(6):1368-1377.
3. Paskett ED, Naughton MJ, McCoy TP, Case LD, Abbott JM. (2007)
The epidemiology of arm and hand swelling in premenopausal breast cancer
survivors. Cancer Epidemiology, Biomarkers & Prevention, 16(4):
775-782.
4. Shah C, Vicini FA (2011) Breast cancer-related arm lymphedema: Incidence
rates, diagnostic techniques, optimal management and risk reduction strategies.
International Journal of Radiation
Oncology·Biology·Physics,81(4):
907-914.
5. Rönkä RH, Pamilo MS, von Smitten KA, Leidenius MH. (2004)
Breast lymphedema after breast conserving treatment. Acta Oncologica.
43(6):551-7.
6. Kwan
ML, Darbinian J, Schmitz KH, Citron R, Partee P, Kutner SE, Hushi LH. (2010)
Risk factors of lymphedema in a prospective breast cancer survivorship study:
the Pathways Study, Archives of Surgery, 145(11):1055:1063.
7. Fu
MR, Guth AA, Cleland CM, Lima ED, Kayal M, Haber J, Gallup L, Axelrod D. (2011)
The effects of symptomatic seroma on lymphedema symptoms following breast
cancer treatment. Lymphology, 44(3):134-43.
8. Ridner SH, Dietrich MS, Stewart BR, et al. (2011) Body mass index
and breast cancer treatment-related lymphedema. Supportive Care in
Cancer 19 (6): 853-7.
9. Finegold D, Baty C, Knickelbein K. (2012) Connexin 47 mutations increase
risk for secondary lymphedema following breast cancer treatment. Clinical
Cancer Research, 18:2382-2390.
http://www.lymphedemablog.com/2012/09/08/the-risk-of-breast-cancer-related-lymphedema-over-time/