Physicians need to be acutely aware of and sensitive to those concerns
and factors that affect quality of life in order to be able to communicate
the necessary information to their patients. Physicians must be able to
provide information to their patients and to place simplistic or incorrect
media reports into perspective.
Patients need to be aware of the side effects and what can be done to
minimize them. They should also realize that some side effects may be due
to other processes, including natural or induced menopause.
As a group, women are sensitive to issues that affect body image; this
is particularly true of breast cancer survivors. Therefore, weight gain
while on tamoxifen may represent a major concern. Menopausal symptoms such
as hot flashes, sleeplessness, and urinary and vaginal changes may be debilitating
and long lasting. Sexual function in the cancer survivor is an issue that
is rarely broached by oncologists. Depression can also occur.
Other risks associated with tamoxifen, such as uterine cancer and ocular
toxicity, are rare, and the role of the drug in the pathology of these
conditions needs to be further defined.
If physicians are aware of patient concerns, communication can be improved.
When patients are adequately informed about the real benefits and risks
of tamoxifen, they are unlikely to refuse treatment and are more compliant
with treatment recommendations.
Tamoxifen is an effective treatment for many women with advanced or
metastatic breast cancer. Recent studies of early-stage breast cancer have
confirmed that tamoxifen, when given after initial surgery or radiation
therapy as "adjuvant systemic therapy," can prevent or delay
breast cancer recurrence.
These studies have also shown that tamoxifen decreases the chance of
breast cancer occurring in the untreated (opposite) breast. Tamoxifen has
also been shown to prevent breast cancer in laboratory experiments. Tamoxifen
is also currently being studied as a preventive treatment for women who
are at an increased risk for breast cancer for a variety of reasons, including
family history, age, and previous history of lobular neoplasia (LCIS or
lobular carcinoma in situ).
Tamoxifen is a hormonal medication that acts against breast cancer cells
by preventing estrogen from binding to the special estrogen receptors that
are present in many breast cancer cells. This interaction inhibits the
growth of cancer cells. Most tumors are tested for estrogen receptors and
their presence determines the likelihood of response to tamoxifen. There
are other mechanisms through which tamoxifen interferes with cancer cells,
some of which are not well understood.
Like all medications, tamoxifen has advantages and disadvantages to
its use. However, for most women with early-stage or operable breast cancer,
the risks of tamoxifen are greatly outweighed by its benefits.
My experience with tamoxifen citrate has been gathered through practice
as a physician. My patients tend to reveal personal concerns to me that
they might not discuss with a male physician. This has put me in a position
to evaluate the benefits and drawbacks of breast cancer treatments from
the patient perspective.
When patients are well-informed, they tend to understand both the benefits
and risks of taking tamoxifen. They know what side effects to expect and
feel a sense of control over their lives. Providing educational materials
such as handouts and videos and referring women to support groups or therapists
are particularly helpful in preparing patients for treatment.
The negative media attention tamoxifen has received lately has created
hysteria in many medical offices. We have to actively debunk negative impressions
patients have developed based on inadequate or misleading information obtained
from the media. We must provide our patients with accurate information
and discuss their concerns in detail in order to help the patient better
manage both their disease and treatment.
Patients easily recognize the benefits of tamoxifen in relation to breast
cancer. I do not have problems explaining these benefits in discussing
why breast cancer patients should take tamoxifen. Clinical trials have
revealed an increase in overall survival as well as disease-free survival
in both premenopausal and postmenopausal patients, particularly those with
estrogen receptor (ER)-positive disease. Data from adjuvant trials have
also demonstrated a 39% reduction in the incidence of contralateral primary
breast cancer with tamoxifen.
Predictors of tamoxifen response include the presence of ER-positive
disease, soft tissue rather than osseous or visceral metastases, older
age, longer time to recurrence, indolent course of disease, and prior response
to hormonal therapy.
Tamoxifen also has favorable secondary effects on bone mineral density
in postmenopausal women and on the cardiovascular system that may not be
as well recognized. The cardiovascular effects are possibly related to
the observed 12% reduction in non-cancer-related mortality. These benefits
may be significant to some women.
Duration of Tamoxifen
The scientific question of how long to give tamoxifen remains unresolved,
but for the patient, it is often a more personal question. Many patients
feel that continuing therapy makes them feel proactive and secure--"the
tamoxifen security blanket."
For patients with node-negative breast cancer, it is relatively clear
that there may be no further benefit in continuing tamoxifen beyond five
years; however, for patients with node-positive disease--and within its
various subgroups--the answer is less clear. Patients with node-positive
breast cancer need to be handled on a case-by- case basis. To formulate
the best plan for the individual patient, we use all the prognostic information
that we have available including pathologic findings, tumor size, number
and level of lymph node involvement, hormonal receptor status, patient
age, and menopausal status. Of course, the patient's preferences must also
Because of the media's inaccurate reporting, the public doesn't understand
the full story about duration and doesn't make the distinction between
node-positive and node-negative disease. Media reports often give the impression
that five years of therapy is standard for all patients, when this is not
the case. Such reports often raise unnecessary concern among patients.
Quality of Life
Side effects of any drug are important to patients in relation to quality
of life, especially when the drug is taken for extended periods. Being
aware of side effects and minimizing their impact are important factors
in continued compliance, which is necessary for maximum effectiveness.
A preliminary investigation was made into the quality of life of tamoxifen
patients participating in the National Surgical Adjuvant Breast and Bowel
Project (NSABP) B-14 protocol (Table 1).
The results demonstrated that there was no major difference between tamoxifen
and placebo in the quality of life: no negative impact on social activities
or work habits, including housework and volunteer work.
More patients receiving tamoxifen experienced hot flashes than those
receiving placebo. Contrary to what I would expect, more placebo patients
reported that they felt less feminine and had reduced sexual desire than
tamoxifen patients. Clearly more quality of life studies with detailed
analyses need to be conducted in breast cancer patients on tamoxifen.
Patients who realize that certain side effects can occur tend to deal
with the side effects better than those who have not been informed prior
to their occurrence. Uninformed patients may not recognize side effects
or seek help. Some patients report that they feel like they are "losing
their mind" and that the side effects are imaginary. Patients must
recognize that the side effects are real.
Types of side effects of tamoxifen vary significantly as does their
reported incidences. As is the norm, patients tend to talk about their
negative experiences rather than their positive ones, so we are more likely
to hear from patients having significant side effects. Discussions on the
Internet and in patient groups also tend to focus on negative experiences,
although occasionally patients report after discontinuing tamoxifen that
they had felt better while on the drug.
Many of the symptoms reported by tamoxifen patients are similar to those
experienced by women going through natural or chemotherapy-induced menopause,
since these symptoms are due to loss of estrogen. Some younger women experience
abrupt, premature menopause on tamoxifen or as a result of chemotherapy
and are very distressed by their symptoms. However, older women seem to
have just as much difficulty.
As do women undergoing menopause, many women on tamoxifen struggle with
hot flashes as well as sleeplessness. Bloating, constipation, irregular
menses, vaginal complaints (dryness, itching, and/or discharge), nonmenstrual
bleeding, depression, memory loss, and hair thinning are also reported.
In many cases it is hard to separate the etiology of the symptoms; the
important thing is to listen and to alleviate symptoms if possible.
Vasomotor symptoms may be remedied by taking vitamin E, B6, or selenium.
Prescription drugs include progesta- tional agents, Bellargal, and clonidine,
the latter two causing major side effects. Using a divided schedule of
tamoxifen or taking it at different times of the day may help to decrease
hot flashes. Incorporation of soy products into the diet several times
a week may be helpful.
Although estrogens are generally contraindicated in breast cancer patients,
some physicians prescribe them to treat estrogen deprivation-related symptoms.
This use of estrogens needs further investigation in controlled clinical
A wide variety of herbal and natural remedies have been used, many without
significant clinical studies on their safety and efficacy (Table
2). Products such as primrose oil, dong quai, cat's claw, blue cohash,
false unicorn root, fennel, thistle, anise, and shark cartilage have been
reported as being used. With some herbs, we do not know why or if they
really help, or if there is a placebo effect. The bioavailability among
preparations may be different. Many of these types of remedies are reported
from patient to patient. When you ask patients what medicines they are
taking, they often do not report all of the additional agents; such remedies
have to be queried about specifically.
Physicians treating breast cancer patients need to be especially sensitive
about the issue of weight gain. Interestingly, weight gain has been correlated
with both menopause and hormone replacement therapy, as well as tamoxifen.
Women in general are concerned about body image, and patients with breast
cancer have just experienced relatively deforming surgery, regardless of
conservation and/or reconstruction, that makes them even more sensitive
to body image.
Weight gain is common in healthy postmenopausal women and is prevalent
in breast cancer patients as a group, regardless of their particular treatment.
My best approach is to tell women that they may gain weight, and I stress
the importance of optimizing their overall health through maintaining good
body weight and exercise, which may prevent osteoporosis and heart disease.
New interest has been generated in a historically neglected issue: sexual
function in the cancer survivor. The lack of estrogen with tamoxifen treatment
causes vaginal dryness, and dyspareunia may result. Painful intercourse
is likely to produce reduced desire and hence sexual avoidance in these
women. In a 1994 abstract, 53% of tamoxifen patients in partnered
relationships reported dyspareunia and 29% reported decreased sexual desire.
A loss of ability to achieve orgasm was suggested by the study. Treatment
with topical estrogens and the use of systemic hormone replacement therapy
in this population is controversial. We recommend the use of a variety
of nonhormonal lubricants (ie, Replens, Astroglide) for this condition.
Vaginal dilators may also prevent or delay vaginal atrophy.
Treatment for reduced sexual desire is less straightforward. The late
Dr. Helen Singer Kaplan attributed reduced libido and sexual responsiveness
in breast cancer survivors, as well as postmenopausal women as a whole,
to reduced circulating testosterone levels.[7,8] She was able to reverse
this condition with low, nonvirilizing doses of testosterone. In addition,
many women are emotionally vulnerable and depressed after breast cancer
diagnosis and surgery, and this has a major impact on sexual life. Antidepressants
and counseling should be considered for these women.
Some reported side effects of tamoxifen are very infrequent, including
dizziness, headache, thromboembolism, and visual changes. Recently, concern
in the media has focused on risks of tamoxifen with respect to the development
of other cancers in breast cancer patients treated with tamoxifen. These
reports have raised concern and need to be discussed openly. It should
be noted that a higher proportion of colon and endometrial cancers have
been reported in breast cancer patients than among the general population.
The actual risks need to be communicated to patients. When patients are
informed about the real risk of developing uterine cancer, they are unlikely
to refuse tamoxifen. Indeed, tamoxifen patients are now monitored more
closely for gynecological symptoms. However, evaluation beyond annual Pap
smears and investigation of nonmenstrual bleeding appear unwarranted.
In postmenopausal women, the benefits of tamoxifen in preserving bone
mineral density is known, although some data imply that there may be bone
loss in premenopausal patients. We should determine whether our patients
have adequate calcium intake with vitamin D and if they are performing
weight-bearing exercise on a regular basis. Bone density evaluation might
be considered in some patients to determine whether further implementation
would be beneficial.
Another rare concern is tamoxifen- associated ocular toxicity. The
pathology of eye findings in tamoxifen patients is very unclear and its
investigation is complicated by age-related eye disease and other medical
illnesses. I recommend baseline eye exams in all my patients.
For women with breast cancer, the benefits of tamoxifen, in terms of
the reduction in contralateral breast cancer and increased survival, clearly
outweigh the risks and toxicity associated with the drug. Despite tamoxifen's
demonstrated efficacy in breast cancer treatment, physicians need to be
concerned about issues that have an impact on a patient's quality of life.
Breast cancer patients are particularly sensitive about body image,
and weight gain on tamoxifen may be a major issue. Menopausal symptoms
such as hot flashes, sleeplessness, and vaginal changes may be prolonged.
Physicians need to broach the subject of sexual function with breast cancer
patients receiving tamoxifen and offer appropriate counsel and/or referral.
In my experience, informing patients about what they can expect from
tamoxifen has made a great deal of difference in their acceptance of treatment.
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3. NSABP Protocol P-1 (Breast Cancer Prevention Trial) May 20, 1992.
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9. Powles TJ, Hickish T, Kanis JA, et al: Effect of tamoxifen on bone
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premenopausal and postmenopausal women. J Clin Oncol 14:78-84, 1996.
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