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322 SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
When patients are first diagnosed with stage
IV breast cancer, a thorough staging must be
performed to delineate the extent of disease,
and a detailed history and physical examination are performed looking to evaluate the
patient’s present symptoms and quality of life.
A biopsy of a metastatic lesion should be considered not only to document true stage IV disease (as compared with a false-positive study)
but also to see if the cancer is hormone-receptor
positive and Her-2/neu positive. The decision to
initiate therapy is then based on both the history and the tumor biology. Patients with minimal symptoms and hormone sensitive tumors
are usually begun on endocrine therapy. There
is no survival advantage to starting chemotherapy orcombined chemotherapy/endocrinetherapy at this point as compared with endocrine
therapy alone.
For patients who have hormone-receptornegative disease or have tumors that are refractory to hormonal therapy, chemotherapy is
considered. This is not mandatory because
patients with minimal symptoms may be
observed. However, patients with tumor-related
symptoms or have a heavy tumor burden (particularly visceral disease) are given chemotherapy. Patients with significant symptoms or in
visceral crisis are started on chemotherapy in
combination with endocrine therapy if they
are hormone sensitive. Patients overexpressing
Her-2/neu are generally started on Herceptin.
The likelihood of responding to chemotherapy depends on several factors, including the
tumor biology, the DFI since initial treatment,
whether adjuvant chemotherapy was used and
what agents, the number of regimens they
have already received for their stage IV disease,
and the sites of the disease. When the disease
progresses in the face of treatment, the regimen is typically changed. Sometimes, patients
who have had extended periods of response or
stable disease may be taken off therapy
(“chemo holiday”). The likelihood of response
and duration of response tends to be greatest
with first-line chemotherapy and decreases
with each subsequent line of treatment.
The median survival for patients with stage
IV breast cancer is typically 2 to 3 years but this
is widely variable and a large number of
patients (as high as 20%) may live for many
years. Although there is no randomized data
comparing chemotherapy to no treatment, the
retrospective data would suggest that survival
is prolonged in patients being treated because
patients who respond tend to live longer than
those who do not. However, although survival
may be prolonged, it is important that patients
understand that cure is highly unlikely.
At some point, the cancer will no longer
respond to treatment and the side effects of
the therapy start to outweigh the benefits. Participation in clinical trials of new agents
remains an option at this point and is generally
strongly encouraged, although patients should
be counseled that these trials are unlikely to significantly alter the course of the disease. Eventually, and this point is different for all
patients, purely palliative or “best supportive
care” may be the most appropriate choice.
Suggested Readings
1. Clemons M, Danson S, Hamilton T, et al. Locore-
gionally recurrent breast cancer: incidence, risk factors and survival. Cancer Treat Rev 2001;27:67–82.
2. Easson AM, McCready DR. Management of local
recurrence of breast cancer. Expert Rev Anticancer
Ther 2004;4(2):219–226.
3. Newman EA,CimminoVM, Sabel MS, etal. Lymphatic
mapping and sentinel lymph node biopsy for
patients with localrecurrence after breast-conservation
therapy. Ann Surg Oncol 2006;13(1):52–57
4. Wright FC, Walker J, Law L, et al. Outcomes after
localized axillary node recurrence in breast cancer.
Ann Surg Oncol 2003;10:1054–1058.
22
Breast Cancer in Special Populations
MALE BREAST CANCER
Clinical Presentation and
Workup
Treatment
Adjuvant Systemic Therapy
BREAST CANCER IN PREGNANCY
Effect of Pregnancy on Breast
Cancer
Diagnosis of Breast Cancer in
Pregnant Women
Breast Cancer in Special Populations: Key Points
Understand the incidence and risk factors for male breast cancer.
Know the surgical and adjuvant treatment for male breast cancer.
Describe your approach to the patient who is pregnant presenting with breast
cancer.
Know when pregnancy is and is not a contraindication to imaging, surgery
and anesthesia, radiation therapy, chemotherapy, or hormonal therapy.
Understand how age may impact decisions in breast cancer treatment.
Know the disparities that exist between African American and Anglo
American women and the possible explanations.
Understand the differences in presentation, histology, and stage of breast
cancer among African Americans compared with Anglo Americans.
Staging
Treatment
BREAST CANCER IN OLDER
PATIENTS
BREAST CANCER AMONG
AFRICAN AMERICAN WOMEN
BREAST CANCER AMONG
OTHER ETHNICITIES
323
324 SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
Male Breast Cancer
Although breast cancer is the most common
malignancy among women, it is extremely rare
among men. In 2008, there were an estimated
1990 new cases of male breast cancer, which
represents only 1% of all breast cancer cases
and 450 deaths. Male breast cancer shares many
of the same characteristics with female breast
cancer, although there are some stark differences. The median age of onset of male breast
cancer is 66, approximately 10 years older than
for females. Several risk factors have been identified for breast cancer in men (Box 22–1). Many
of these are related to alterations in estrogen/
androgen balance because androgens appear
to have a protective effect on breast tissue by
inhibiting cell proliferation. However, the relationship between hormones and male breast
cancer is not clear because men with breast cancer do not exhibit abnormalities in peripherally
detectable hormone levels. In addition, other
conditions that result in increased estrogen,
such as obesity, thyroid disease, marijuana use,
or exogenous estrogen use do not seem to
increase the risk of breast cancer.
A family history of breast cancer is present in
approximately 15% to 20% of cases. Breast cancer gene (BRCA) 2 mutations are associated
with a 6% lifetime risk of male breast cancer,
which might not sound high compared to the
risk in females, but represents a 100-fold higher
risk compared to the general population. BRCA2
mutations are responsible for between 5% and
15% of male breast cancers. BRCA1 mutations
do not have as significant a role. Male breast
cancers in BRCA2 carriers may exhibit a more
BOX 22–1 RISK FACTORS FOR
MALE BREAST CANCER
Gynecomastia or previous benign
breast disease
Jewish ancestry
Family history of breast cancer
Previous chest wall irradiation
Testicular disease (orchitis,
cryptorchidism, congenital inguinal
hernia, infertility, orchiectomy, injury)
Liver disease (cirrhosis, alcoholic liver
disease, schistosomiasis)
Klinefelter syndrome
Prolactinoma
Breast cancer gene (BRCA) 2 mutation
Cowden syndrome (PTEN mutation)
aggressive phenotype, with higher grade and
overexpression of human epidermal growth factor receptor 2 (Her-2/neu). A mutation in the
tumor suppressor gene PTEN, which is associated with Cowden syndrome, or the mismatch
repair gene hMLH1 have also been reported in
patients with male breast cancer, although
whether or not there is a causal relationship
remains unclear.
Clinical Presentation and Workup
The typical presentation of male breast cancer
is that of a painless, firm subareolar mass. Less
commonly, it may present as a mass in the
upper, outer quadrant. Because there is minimal breast tissue, the nipple is commonly
involved (ulceration, retraction) although nipple discharge is rare. The mass may be fixed to
the overlying skin or underlying muscle. The
differential diagnosis would include gynecomastia, infection (abscess), or a nonbreast primary such as sarcoma.
Mammogram is helpful, being abnormal in
80% to 90% of cases, and can help differentiation between gynecomastia and breast cancer. However, false-negatives do occur and so
a tissue diagnosis is warranted for any suspiciousmassinthebreast.Thisshouldbe
either a core biopsy or open biopsy because
fine-needle aspiration (FNA) c an be inaccurate. Invasive ductal carcinoma represents
more than 90% of cases; invasive lobular is
rare. Ductal carcinoma in situ (DCIS) is also
rare in men. Over 90% of male breast cancers
express estrogen receptor (ER) and progesterone
receptor (PR). The her-2/neu protooncogene is
less likely to be overexpressed in men than in
women. Staging workup is similar to that of
female breast cancer. A full history and physical
should be performed looking for signs or symptoms of metastatic disease. Ultrasound of the
breast and axilla are often performed because
sentinel lymph node (SLN) biopsy can be
avoided if an ultrasound-guided FNA can document nodal metastases preoperatively. Computed tomography (CT) scan and bone scan
should be obtained if the patient has signs or
symptoms suggestive of metastatic disease.
Treatment
Localized male breast cancer is treated by mastectomy. Radical mastectomy should not be
necessary unless there is extensive chest wall
involvement. Given the lack of breast tissue
32522—BREAST CANCER IN SPECIAL POPULATIONS
and central location of the tumors, breastconserving therapy (BCT) is not typically considered. Radiation is typically not recommended
after mastectomy, although recommendations
have been made to use postmastectomy radiation therapy for the same indications you would
use in women (locally advanced disease or multiple positive axillary nodes) to decrease the likelihood of locoregional recurrence.
The management of the axilla has changed
with the advent of SLN biopsy. Although modified radical mastectomy has been the standard, SLN has been shown to be successful in
men as well and may spare the morbidity of
axillary lymph node dissection (ALND) for
patients who are node negative. Patients with
a positive sentinel node should have a complete lymph node dissection. As with female
breast cancer, the number of positive nodes
correlates with survival. Patients with histologically negative nodes have a 10-year diseasespecific survival between 77% and 84%. This
drops to around 50% with one to three positive nodes and 14% to 24% for four or more
positive nodes (Table 22–1).
Adjuvant Systemic Therapy
The recommendation for adjuvant therapy is
based largely on the benefits seen in women
and small retrospective reports (compared to
historical controls) because breast cancer in
men is too uncommon to perform randomized
trials. Because the majority of cases are hormonereceptor positive, 5 years of adjuvant tamoxifen is frequently recommended. However, men
have more difficulty than women tolerating
the side effects and may not last the full 5 years
(Box 22–2). Chemotherapy is also typically
recommended for men at high risk of recurrence as it is in women, although chemotherapy
BOX 22–2 SIDE EFFECTS OF
TAMOXIFEN IN MEN
Decreased libido
Weight gain
Hot flashes
Mood alteration
Depression
appearstobeusedlessofteninmenwhencompared stage by stage. The indications are the
same as for women, node-positive disease or
tumor size greater than 1 cm. Chemotherapy
should also be considered for men with hormone-receptor-negative disease. Her-2/neu and
p53 expression have been associated with poor
prognosis and may push toward more aggressive
systemic therapy. The choice of agents is also
similar to women, with anthracycline-based chemotherapy for patients who are node negative,
and anthracyclines and taxanes for patients
who are node positive.
With adequate therapy, the 5-year survival by
American Joint Committee on Cancer (AJCC)
tumor stage is between 80% and 100% for stage
I disease, 65% to 80% for stage II disease, 25%
to 60% for stage III disease, and between 0%
and 25% for stage IV disease. Although in the
past breast cancer was considered more aggressive in men than in women, the most recent
data suggests that when matched for stage and
grade, there is not a significant difference in
outcome between genders.
In patients with metastatic disease, if they are
still receptor positive, hormone therapy should
be considered the first-line treatment with systemic chemotherapy reserved for second-line
treatment. Hormone therapy can be medical
(tamoxifen, megestrol acetate, androgens, steroids) or surgical (orchiectomy, adrenalectomy,
TABLE 22–1Disease-Specific and Overall Survival Rates in Male Breast Cancer
From 1,986 Patients in the Surveillance, Epidemiology and End Results Database,
1988–2001
Stage I Stage II Stage III Stage IV
Disease-specific survival (%)
5 year 96 88 60 23
10 year 93 74 44 21
Overall survival (%)
5 year 78 66 39 14
10 year 55 39 21 5
From Giordano SH. A review of the diagnosis and management of male breast cancer. The Oncologist
2005;10:471-479.
326 SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
or hypophysectomy). For patients who are ER
positive, tamoxifen has a higher response rate
than the other therapies with a better side-effect
profile. In patients who progress following
tamoxifen treatment, these alternative endocrine therapies should be considered. Although
bilateral orchiectomy is effective, many men
are unwilling to opt for this. The role of aromatase inhibitors (AIs) is unclear. Chemotherapy
should be used in patients who are ER negative
or patients who are ER positive and not responding to hormonal therapy.
Breast Cancer in Pregnancy
A challenging and not infrequent dilemma is
the management of breast cancer in pregnant
women. Breast cancer is the second most common cancer associated with pregnancy (cervical
cancer is first) with an incidence of approximately 1 in 3000 pregnancies. The incidence of
pregnancy-associated breast cancer is likely to
increase as more women delay childbearing
given the increased incidence of breast cancer
with increasing age.
Effect of Pregnancy on Breast Cancer
The relationship between pregnancy and
breast cancer risk is complex. Overall, a younger age at first live birth is associated with a
lifetime risk of breast cancer. Having a pregnancy before age 20 reduces lifetime risk by
approximately 50%. However, although there
may be a long-term protective effect on the
development of breast cancer with pregnancy,
pregnancy itself may result in a transient
increase in risk. Two population based studies
have demonstrated an increased risk of breast
cancer for 3 to 15 years after pregnancy followed by a subsequent decline. This transient
risk appears to be most apparent among
women who are older at the time of their first
delivery. How can this be? Although it is not
exactly known, it may be that the hormones
associated with pregnancy can stimulate the
growth of cells in the early stages of malignant
transformation and may also induce the differentiation of normal mammary stem cells that
would have had the potential for neoplastic
change in the future. Therefore, premenopausal women who have early premalignant
changes (more likely among older premenopausal women) may see pregnancy accelerate
that transformation. The remainder of women
lose a portion of those undifferentiated cells
that may ultimately become breast cancer,
decreasing their long-term risk (Chapter 1).
Diagnosis of Breast Cancer in Pregnant Women
Delay in diagnosis contributes significantly to
the worse outcome typically associated with
breast cancer during pregnancy. As with nonpregnant women, the typical presentation is a
mass in the breast, but the physiologic changes
(engorgement, hypertrophy) may delay both
the patient and physician from detecting a
mass. It is not uncommon for physicians to
assume the mass is benign or delay biopsy until
after pregnancy, but even a 1 month delay in
diagnosis can increase the risk of nodal involvement. Therefore, the index of suspicion must be
high for any pregnant or postpartum woman
presenting with a palpable mass. Mammography can be performed safely in pregnant
women with abdominal shielding. Although
the use of mammography is hampered by the
increased water content, higher density, and
loss of fat in the breast during pregnancy, it
can still be useful. A negative mammogram,
however, should not dissuade your suspicion
because false-negative mammograms are not
uncommon. Ultrasound can be particularly
helpful for differentiating cystic from solid
lesions. Magnetic resonance imaging (MRI) is
possible because it is used for fetal imaging during pregnancy with no suggestion of adverse
sequelae on the fetus, although the data on the
effectiveness on MRI of the breast during pregnancy is lacking. In addition, gadolinium contrast, which is often used to differentiate
benign from malignant lesions in breast MRI,
crosses the placenta and causes developmental
abnormalities in animal models.
There is no excuse not to biopsy a clinically
suspicious mass in a pregnant female. Fineneedle aspiration (FNA) is more difficult to interpret, but in the hands of a skilled cytopathologist
(who knows the specimen comes from a pregnant woman) it can be accurate. Core biopsy
can be safely performed under local anesthesia,
and although milk fistula has been described, it
is extremely rare. Both incisional and excisional
biopsy can also be performed safely.
Staging
Women with pregnancy-associated breast cancer tend to present with worse prognostic signs
(ER/PR negative, high grade) and more advanced
32722—BREAST CANCER IN SPECIAL POPULATIONS
stage than nonpregnant women (larger tumors,
higherfrequency of nodal or distant metastases).
It is unclear if this is more related to delay in
diagnosis than a more aggressive biology. It
is also unclear if, when controlling for all prognostic factors, breast cancer during pregnancy
has a worse outcome. It is important, however,
to accurately stage the patient when planning
therapy. The initial staging examination should
be similar to that in nonpregnant women, with
a thorough history and physical. Ultrasound
of the axilla with FNA of any clinically suspicious nodes should be considered. The indications for a complete staging workup are the
same as in nonpregnant women, reserved for
women with clinical positive nodes, T3 or
T4 tumors, or symptoms suggesting distant
disease. Computed tomography (CT) scans
should be avoided during pregnancy because of
the large cumulative radiation dose. Chest
Pregnant patient with breast cancer
1st
trimester
No evidence of distant spread
x-ray is safe with abdominal shielding, although
limited in visualizing the lower lung parenchyma late in gestation. Theliver should be evaluated with an abdominal ultrasound. MRI can
be used for further evaluation if necessary. Bone
scans can also be obtained during pregnancy if
necessary, however the patient should be adequately hydrated and have a Foley catheter for
8 hours to prevent retention of radioactivity in
the fetus.
Treatment
As with nonpregnant women, the goal of therapy is both the local and systemic control of disease (Fig. 22–1). The impact of those treatments
on the fetus must be strongly considered.
Treatment should be coordinated with a specialistinmaternalandfetalmedicinetomonitor
the pregnancy. The gestational age and expected
Rule Out Distant Disease
If needed:
Late 3rd
trimester
Strongly
desires BCT
Consider
therapeutic
abortion
Figure 22–1. Approach to the pregnant patient with breast cancer. The primary goal is to avoid radiation
while the patient is pregnant and a long treatment-free delay between surgery and radiation. Chemotherapy
may be used but only based on the risk of systemic disease and not to provide a bridge to radiation that allows
breast-conserving therapy.
Mastectomy
SLN (radiotracer only)
or ALND
Delivery would
precede XRT
Mastectomy or
lumpectomy
SLN (radiotracer only)
or ALND
Adjuvant chemotherapy if indicated
Radiation therapy and/or hormonal therapy after
delivery, if necessary
Chemotherapy
2nd or early 3rd
trimester
not clearly
indicated
XRT would
precede delivery
Mastectomy
SLN (radiotracer only)
or ALND
Chemotherapy
clearly indicated
Mastectomy or Lumpectomy
Preoperative
chemotherapy
Mastectomy or lumpectomy
Radiation therapy and/or
hormonal therapy after
delivery, if necessary
Adjuvant chemotherapy,
radiation therapy and/or
ALND
SLN (radiotracer only)
or ALND
hormonal therapy after
delivery
328 SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
date of delivery will be important pieces of information in planning therapy. Amniocentesis
may be necessary to determine pulmonary
maturity.
When pregnant women are diagnosed with
breast cancer, one option is to terminate the
pregnancy. However, breast cancer can be successfully treated during pregnancy, and early
termination does not improve the outcome
of the breast cancer.
Surgery can be performed safely in pregnant
women when planned with both anesthesiology and obstetrics (Box 22–3). Therefore, there
is no contraindication to performing a modified radical mastectomy (MRM) in a pregnant
woman. However, pregnant women are often
just as motivated to conserve the breast and
avoid ALND as nonpregnant women. Unfortunately, radiation therapy to the breast, an
important component of BCT, is contraindicated during pregnancy. The risk to the fetus
BOX 22–3 ANESTHETIC CONCERNS
IN THE PREGNANT PATIENT
Altered physiology of pregnancy
Increased blood volume with physiologic
anemia
Increased heart rate and cardiac output
Elevated diaphragm, decreased
functional residual capacity
Increased oxygen consumption
Decreased partial pressure of carbon
dioxide (pCO
capacity, and normal acid-base balance
(pH)
Increased fibrinogen and platelet count
Prolonged gastric emptying and
increased risk of aspiration
Use of oral noncolloidal antacids and
Reglan
Rapid sequence induction with cricoid
pressure
Hypotension resulting from aortocaval
compression
Left lateral tilt with 15-degree wedge
under right hip
Maternal hyperventilation and fetal
acidosis
Monitor fetal heart rate, avoid
hyperventilation, and maintain normal pH
Risk of preterm labor
), decreased buffer base
2
is high because it cannot be adequately
shielded. If a woman wishes to pursue breast
conservation, she has several options.
If the cancer is detected in the third trimester,
or the late second trimester, she may undergo
lumpectomy and defer the radiation until after
delivery. If, based on the stage of the cancer,
she will require systemic chemotherapy, this
will delay the implementation of radiation
therapy up to 6 months. This may allow
women in the first or second trimester to opt
for breast conservation. Neoadjuvant chemotherapy can also be considered when appropriate. This results in a catch 22 because women
who have smaller cancers early in the pregnancy will more often require mastectomy
because they do not require adjuvant chemotherapy and thus would have an unacceptable
delay between lumpectomy and radiation.
Women in this situation may consider this
option; however, they may be exposing themselves to a higher local recurrence rate.
Pregnant women who are clinically node
negative may undergo SLN biopsy for axillary
staging. The procedure should be done with
radiolabelled colloid only and not isosulfan
blue dye secondary to the risk of allergic reaction. The radiolabelled colloids are associated
with a minimal dose of radiation exposure to
the fetus as a result of the rapid uptake in the
maternal reticuloendothelial system.
Although there are increased risks, adjuvant
chemotherapy can be administered to pregnant women with breast cancer (Box 22–4).
Potential agents include cyclophosphamide,
doxorubicin, and 5-Fluorouracil (5-FU). Methotrexate is contraindicated. Chemotherapy
should not be administered during the first trimester because there is an increased risk of
abortion and malformations. Beyond the first
BOX 22–4 RISKS OF
CHEMOTHERAPY ON THE FETUS
AND NEONATE
Immediate risks
Spontaneous abortion
Teratogenesis
Premature birth or low birth weight
Possible complications secondary to in
utero exposure
Carcinogenesis
Sterility
Delayed physical or mental growth
Mutation
32922—BREAST CANCER IN SPECIAL POPULATIONS
trimester, chemotherapy does not appear to
increase the risk of fetal abnormalities. The
optimal timing would have chemotherapy
conclude 4 weeks before delivery, so that
decreased blood counts do not lead to bleeding
or infectious complications. However, a careful
discussion needs to be held with the patient
regarding the risks and benefits of adjuvant
chemotherapy. Adjuvant chemotherapy may
be associated with intrauterine growth restriction and prematurity. In addition, there is little
long-term data on children exposed to chemotherapy in utero. Endocrine therapy, particularly tamoxifen, is contraindicated during
pregnancy. Postpartum tamoxifen can be considered for use in hormone-receptorpositive tumors.
Breast Cancer in Older Patients
The current median age at diagnosis for breast
cancer is 61, and most of the women who die
of breast cancer are overthe ageof 65.As thepopulation grows and ages, new breast cancer cases
increase as the incidence of breast cancer rises
with age. It is therefore not surprising that an
individual surgeon’s practice will continue to
see an increasing percentage of breast cancer
patients in their 70s and 80s. It is therefore important to understand how to approach the
elderly woman with breast cancer, knowing
when age should factor into surgical decision
making and when it should not.
When compared to their younger counterparts, breast cancers in older women tend to
have different biologic characteristics. Breast
cancers in older women are more often of a
lower grade, are ER/PR positive, and associated
with a decreased expression of poor prognostic
markers such as Her-2/neu. They are also less
likely to involve the regional nodes. Despite
the fact that older women are often treated less
aggressively, their prognosis is good. In a study
of tumor biology and outcome from the Surveillance, Epidemiology and End Results (SEER)
database, women over 70 with node-negative
tumors had an 8-year overall survival rate comparable to an age-matched population without
breast cancer. Women with node-positive
tumors had only a modest decrease in overall
survival. This is despite the fact that older
women had lower rates of surgery, radiation,
and chemotherapy than younger patients.
Although this would imply that breast cancers
in older women have a more indolent course,
that statement is certainly controversial and
could lead to undertreatment of the elderly population, resulting in excessive local, regional,
and distant recurrence.
Certainly, when looking at the older population as a whole, there is a decreased overall survival and an increased risk of death from
causes other than breast cancer, and this must
be taken into account when reviewing treatment options. However, the clinician must also
take into account that overall patients are living
longer, thus a healthy older patient may have a
longer period to develop recurrence than just
10 years ago. It is therefore not correct to say
that simply because a patient is over 70 or 75 it
is reasonable to offer less aggressive therapies.
Instead, when facing an individual elderly
patient with breast cancer, their chronologic
age should be secondary, and their physiologic
age should be examined. This would include
looking at their functional status, comorbidities,
and life expectancy. In this manner, the risks
and benefits of surgery and adjuvant therapy
can be more accurately weighed. There are several tools that may be useful in this situation.
The Eastern Cooperative Oncology Group
(ECOG) and Karnofsky performance scales are
often used to identify patients with decreased
functional status and hence worse outcomes
with therapy (Tables 22–2 and 22–3). The com-
prehensive geriatric assessment (CGA) is a
structured evaluation of elderly patients on multiple levels including physical and functional
status, comorbidities, nutritional status, and
TABLE 22–2Eastern Cooperative
Oncology Group (ECOG) Performance
Status Criteria
Grade Status
0 Fully active, able to carry on all predisease
performance without restriction
1 Restricted in physically strenuous activity
but ambulatory and able to carry out
work of a light or sedentary nature (e.g.,
light housework, office work)
2 Ambulatory and capable of all self-care
but unable to carry out any work
activities; up and about more than 50%
of waking hours
3 Capable of only limited self-care;
confined to bed or chair more than 50%
of waking hours
4 Completely disabled; cannot carry on any
self-care; totally confined to bed or chair
5 Dead
330 SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
TABLE 22–3Karnofsky Performance
Status
Grade Karnofsky Scale
100 Normal, no complaints; no evidence of
disease
90 Able to carry on normal activity; minor
signs or symptoms of disease
80 Normal activity with effort; some signs or
symptoms of disease
70 Cares for self but unable to carry on
normal activity or to do active work
60 Requires occasional assistance but is able
to care for most personal needs
50 Requires considerable assistance and
frequent medical care
40 Disabled; requires special care and
assistance
30 Severely disabled; hospitalization is
indicated, although death is not
imminent
20 Very ill; hospitalization and active
supportive care are necessary
10 Moribund
0 Dead
geriatric syndromes such as dementia or
depression. It may also be useful to assess these
patients in a multidisciplinary or tumor board
setting, to gain the input of medical oncologists and radiation oncologists before
planning surgical therapy.
If your assessment of the elderly patients
reveals a healthy woman with minimal functional limitations, then the surgical options
are no different than the younger patient. Primary surgery can be either mastectomy or
BCT. Morbidity and mortality rates of mastectomy in older patients are comparable to younger patients, although there is clearly some
selection bias. It is important to remember that
age is not a contraindication to BCT. Although
some studies demonstrate that older women
have lower rates of breast conservation, when
older women are presented with both options
they are just as likely to prefer breast conservation as younger women. To assume an older
woman cares less about body image and the
psychosocial implications of mastectomy
would be incorrect, and surgeons should offer
the two surgical options in the same manner
as they would a younger woman.
For elderly women with larger primary
tumors who still desire breast conservation,
neoadjuvant therapy also remains an option.
If there is a concern regarding neoadjuvant chemotherapy in this population, an alternative
approach might be neoadjuvant hormonal
therapy. In older patients who are hormonereceptor positive, neoadjuvant hormonal therapy with tamoxifen, anastrozole, or letrozole
have been reported to have clinical response
rates similar to those seen for chemotherapy.
Thesamerecommendationshouldbemade
for axillary evaluation. It has been suggested
that because older women are less likely to
be node positive and have decreased overall
survival, that axillary evaluation with SLN
biopsy may not be necess ary. However, knowing whether an elderly patient is node positive or node negative may significantly
change recommendations for adjuvant therapy, and SLN biopsy has few side effects in
older women. This is an example in which
the multidisciplinary approach is quite useful
because the medical oncologist can weigh in
on whether systemic therapy might change
with the information gleaned from a SLN
biopsy.
A more controversial issue is the management of the elderly patient with the positive
SLN. Although the standard of care is a complete ALND, the overall survival benefit of
the complete ALND is unknown for all
patients with breast cancer, let alone older
patients, and older women tend to have worse
quality of life scores and difficulties with function after ALND. However, even in the absence
of an overall survival benefit, there may be a
benefit to regional control. Predictive models
and nomograms can help assess an individual
woman’s risk of harboring additional disease
in the nonsentinel lymph nodes, and this
information can be used for a balanced discussion with the patient regarding the relative
pros and cons of completing the ALND in the
elderly patient with breast cancer who is SLN
positive.
Another area of discussion is whether radiation is a necessary adjunct to lumpectomy
among older women. Radiation therapy is well
tolerated in elderly patients, and there is no
doubt that radiation will decrease in-breast
recurrences after lumpectomy and chest wall
recurrences after mastectomy. Overall, the
decreased local recurrence rates associated with
radiation will impact overall survival (see
Chapter 15), although most of these trials had
upper age cutoffs. Therefore, there has been
some question to the benefit of radiation therapy in the elderly population. Two randomized
33122—BREAST CANCER IN SPECIAL POPULATIONS
studies addressed this issue. In a randomized
trial of radiation therapy compared to no radiation therapy in 796 patients over the age of 50,
radiation had no impact on overall survival but
did decrease local recurrence rates from 7.7% to
0.6% (p < 0.001). In a study limited to women
who were hormone-receptor positive over the
age of 70, radiation decreased locoregional
recurrence from 4% to 1% (p < 0.001) but again
had no impact on distant disease-free or overall
survival. It may, therefore, be reasonable to
offer lumpectomy alone to a subset of older
women, omitting radiation therapy. This decision should be based on multiple factors
including the woman’s life expectancy, functional status, ability to go through radiation,
tumor size, hormonal status, and lymph node
status. Again, the tumor board approach is particularly helpful and may impact the surgical
decision making if lumpectomy alone is a
consideration.
When faced with an elderly patient with
moderate to significant comorbidities, it can
sometimes be difficult to judge how aggressive
to be in managing their breast cancer. In
patients who are not good candidates for surgery, hormonal therapy alone is often used if
the patient is hormone-receptor positive. In
randomized trials of primary endocrine therapy versus surgery, overall survival is similar,
however, locoregional control is significantly
worse. Even among patients with advancing
age and comorbidities, both lumpectomy and
mastectomy are well tolerated and many
patients treated with hormone therapy alone
will ultimately require surgery for local control. They may end up being worse candidates
for surgery when that time comes. Therefore,
endocrine therapy alone should be reserved
for patients with significant comorbidities for
whom surgery would carry excessively high
risks.
Finally, the most controversial aspect of breast
cancer care among the elderly is the use of systemic adjuvant therapy. The benefits of adjuvant
therapy for breast-cancer-specific prognosis
must be weighed against the treatment related
toxicity and the nonbreast-cancer prognosis.
Clinical trial data is limited as many prospective,
randomized trials failed to accrue significant
numbers of elderly patients. The Early Breast
Cancer Trialists’ Collaborative Group (EBCTCG)
has performed a meta-analysis on a large number of clinical trials, allowing for analysis of
small subsets including the elderly, and much
of the basis for systemic therapy in the elderly
comes from this data.
For hormone-receptor-positive tumors, selective estrogen receptor modulators (SERMs) and
aromatase inhibitors (AIs) clearly reduce recurrence and mortality and are well tolerated in
the elderly population. Unless the patient has
an extremely good-prognosis tumor or significant comorbidity that precludes it, hormonal
therapy should be strongly considered. Tamoxifen can reduce breast cancer mortality by 31%
in postmenopausal women, regardless of age,
and the side effects (vasomotor symptoms,
endometrial cancer, thromboembolic disease)
are infrequent and do not significantly contribute to the likelihood of dying of nonbreast cancer causes. AIs are slightly better than
tamoxifen, improving disease free survival by
3% to 5%. This effect was most pronounced in
women over 64 years of age. For women who
took 5 years of tamoxifen, the addition of letrozole improved overall survival in patients who
were node positive. For women who took 2 to
3 years of tamoxifen, switching to an AI, as
opposed to staying on tamoxifen for the full 5
years, improved disease-free survival. Therefore
postmenopausal women should have an AI as
part of their hormonal therapy, although which
agent and when to introduce it is less clear. The
major complication of the AIs is musculoskeletal complications, including osteoporotic fractures. These women should undergo baseline
and yearly bone densitometry.
Adjuvant chemotherapy decisions are more
difficult because there is a smaller benefit and
more side effects to consider. This includes the
addition of chemotherapy to hormonal therapy
in patients who are hormone-receptor positive
and the systemic options for patients who are
hormone-receptor negative. Even if a benefit is
present, the side effects of chemotherapy can
be more significant in older women. Myelosuppression and neutropenic infections increase
with age. Age isa known risk factorfor anthracycline-associated cardiac toxicity, and age is associated with higher rates of cardiomyopathy in
women treated with chemotherapy. An
increased mortality rate secondary to chemotherapy has been reported in older women,
which may offset some of the benefit. It is hard
to truly study this, even prospectively, because
of the selection bias in entering older women
onto clinical trials(as a result of both strict entry
criteria and physician bias). The EBCTCG
overview is limited by the small number of
women over 70 in the clinical trials and the lack
of data regarding newer agents. However, it
seems unlikely that elderly women with
node-negative disease would benefit from