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Treatment of Estrogen Deficiency Symptoms in Women Surviving Breast Cancer, Part 4

Treatment of Estrogen Deficiency Symptoms in Women Surviving Breast Cancer, Part 4

ABSTRACT: There are several million breast cancer survivors worldwide. In the United States, 180,000 women were diagnosed with breast cancer in 1997, and approximately 97,000 of these women have an extremely low chance of suffering a recurrence of their cancer. With an average age at diagnosis of 60 years and a 25-year expected duration of survival, the current number of breast cancer survivors in the United States may approach 2.5 million women. Since breast cancer is now being detected at an earlier stage than previously and since adjuvant chemotherapy may cause ovarian failure, an increasing number of women are becoming postmenopausal at a younger age after breast cancer treatment. This conference was convened in September 1997 to consider how menopausal breast cancer survivors should be treated at the present time and what future studies are needed to develop improved therapeutic strategies. A total of 47 breast cancer experts and 13 patient advocates participated. The proceedings of the conference are being published in six installments in successive issues of oncology. This fourth part focuses on the treatment of urogenital atrophy, vasomotor instability, sleep disorders, and other related symptoms. [ONCOLOGY 13(4):551-575,1999]

Proceedings of a Conference, Held at the Boar's Head Inn, Charlottesville,Virginia, September 21-23, 1997

Frequency of Symptoms in Women With Breast Cancer

Patricia Ganz, MD: I will discuss two different studies
focusing on the frequency of vasomotor symptoms and urogenital
atrophy, respectively, in women surviving breast cancer. One study
involved breast cancer patients recruited from the Los Angeles
community and followed longitudinally during the first year after
diagnosis.[1] The second study, conducted in Washington, DC, and Los
Angeles, was a large, cross-sectional survey of breast cancer
patients who were disease-free between 1 and 5 years after diagnosis.[2]

Symptom Profiles

In the first study, the average age of patients was 55 years; most
had partners and were very well educated; and their ethnic
distribution was representative of the breast cancer population in
Los Angeles. Patients were interviewed at 1, 4, 7, and 13 months
after diagnosis regarding their symptoms related to the climacteric.

For the purpose of this presentation, I have divided the sample into
three age groups: women < 50 years; those 50 to 59 years old; and
those ³ 60 years old. In women <
50 years of age, there was a relatively low rate of hot flashes at 1
month after diagnosis, with an increase to 45% at 7 months and a
slight decline by 13 months. These findings likely represent the
effect of chemotherapy in inducing premature menopause in these
younger women.

The severity of hot flashes increased in women under age 50 as a
function of time since surgery. For women over 50 years old, hot
flash severity remained stable over the course of the 1 year of
observation. These findings suggest that breast cancer treatment has
an impact on ovarian function in younger women, but no hormonal
changes probably occur in the older group.

It is likely that most women 50 to 59 years old had already entered
menopause at the time of their breast cancer diagnosis. Many of these
women could have been receiving hormone replacement therapy (HRT) at
the time of diagnosis and stopped it thereafter. Some of these women
(35%) were already experiencing vasomotor symptoms at 1 month after
surgery; these symptoms increased in frequency at 7 months (60%) and
persisted over the course of 1 year (55%).

Symptoms due to vaginal lubrication problems were available from
sexually active women only. High rates of these problems were
reported 1 month after surgery for all women independent of age (<
50 years old, 50%; 50 to 59 years old, 52%; ³
60 years old, 57%), and these high rates persisted for up to 1 year.
Since many of these women were postmenopausal at diagnosis, one
cannot conclude that the therapy initiated for breast cancer
treatment was causative. This finding led to more detailed studies
focused on sexuality and intimacy in breast cancer survivors.[2] The
older women stated that the severity of sexual problems was greatest
early after diagnosis, with an improvement during the year of
follow-up. Regardless of age, all women reported nearly the same
severity of symptoms (hot flashes, lubrication problems) when
evaluated at 1 year.

Sexual Functioning

In additional analyses of the same study sample,[1] we used the
Cancer Rehabilitation Evaluation System (CARES) Sexual Functioning
Scale (an 8-item measure) to assess sexual functioning. The youngest
women reported the most disruption in sexual functioning initially
after surgery; this improved somewhat over time but was still a
persistent problem at 1 year. In the women 50 to 59 years old, sexual
functioning scores at 1 month after surgery were intermediate between
the youngest and oldest women, and their functioning did not change
over time. In contrast, women over 60 years of age reported better
sexual functioning initially (many were not sexually active with a
partner), and this did not change over time.

These findings suggest that sexual functioning is disrupted to the
greatest extent in the younger women, and that the reported
dysfunction does not seem to recover after the breast cancer
experience (ie, it does not improve with time since diagnosis).

Sexuality and Intimacy in Breast Cancer Survivors

In the second cross-sectional study,[2] our research group addressed
the question of sexuality and intimacy in breast cancer survivors,
with a special focus on whether sexual functioning would improve
somewhat later after the breast cancer diagnosis. We reported on data
from a large cross-section of disease-free patients living in Los
Angeles and Washington, DC (N = 864).[2] On average, these women
completed the survey 3 years after their breast cancer diagnosis. The
women in this sample were similar medically and demographically to
those in the first study.[1]

One issue that was addressed in this survey was the frequency of
menstruation after breast cancer and the history of use of HRT. Only
a small number of women continued to menstruate after their breast
cancer diagnosis, and many (36%) had used HRT before being diagnosed.
There was a divergence in HRT use between women living on the East
and West coasts; a larger proportion of Los Angelean women reported a
history of HRT use.

A symptom checklist was used to assess menopausal symptoms in this
study sample. As shown in Figure 1,
the prevalence and severity of hot flashes increased with age, and
these symptoms were more frequent in the breast cancer survivors than
in healthy volunteers participating in the National Surgical Adjuvant
Breast and Bowel Project (NSABP) Breast Cancer Prevention Trial
(baseline data obtained prior to randomization to tamoxifen
[Nolvadex] or no tamoxifen).[3]

The breast cancer survivors who were < 60 years old appeared to
show the greatest differences from the healthy comparison group. Hot
flashes were less of a problem in women over 60 years old, but their
severity was greater in the women with breast cancer than in
controls. Although hot flashes were reported more frequently in
breast cancer survivors, they were not extraordinarily severe.

With respect to urinary incontinence, the frequency of this complaint
increased with increasing age (< 50 years old, 16%; 50 to 59 years
old, 35%; ³ 60 years old, 40%). In
both normal healthy women and those treated for breast cancer, these
symptoms were not extremely severe.

When asked about vaginal dryness, only 20% of younger (35- to
49-year-old) healthy women reported this problem vs 45% of younger
breast cancer survivors. The same trend was seen in older women, with
breast cancer survivors reporting this problem more frequently.

Similar trends were noted with respect to pain during intercourse;
younger healthy women reported less pain than did age-matched women
surviving breast cancer. This symptom increased with age in both the
healthy women and breast cancer survivors.

Sexual Functioning andQuality of Life

There is a similarity between our findings on sexual functioning in
breast cancer survivors and data obtained from the Postmenopausal
Estrogen/Progestin Intervention (PEPI) trial in healthy
postmenopausal women.[4] When comparing our database with the PEPI
data, age-matched scoring of sexual dysfunction scales did not differ
between the two groups.[2] Both groups experienced a decline in
sexual functioning with age.

Based on this finding, it is difficult to attribute most sexual
dysfunction to therapy for breast cancer, as opposed to the normal
effects of aging. This must be taken into account when conducting
studies of sexual functioning in breast cancer survivors.

In addition, quality-of-life scores of breast cancer survivors on the
Medical Outcomes Study, Short Form-36 (MOS SF-36) were equal to or
better than scores of healthy, age-matched, control women.[2] These
observations suggest that although breast cancer has an important
effect on women’s lives, it does not translate into apparent
decrements in their quality of life, as measured by standardized instruments.

Using data from this large cross-sectional sample, our group
developed a model for examining sexual functioning that takes into
account factors affecting women with breast cancer (eg, type of
surgery, body image, chemotherapy, use of tamoxifen). In this
multivariate model, the use of chemotherapy, discomfort with body
image, and the presence of hot flashes predicted for poorer sexual
functioning. Tamoxifen use was not associated with worse sexual functioning.

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