2005 The results of treatment of epithelial ovarian cancer after centralisation of primary surgery. Results from North Jutland, Denmark

Gynecol Oncol, September 6, 2005;

Erik Soegaard Andersen, Aage Knudsen, Tove Svarrer, Bente Lund, Kirsten Nielsen, Anni Grove, and Mette Tetsche
Department of Obstetrics and Gynecology, Oncologic Section, Aalborg University Hospital, Denmark.


OBJECTIVE.: The study was performed to evaluate the results of treatment of ovarian carcinoma after the introduction of centralised primary surgery in the County of North Jutland, Denmark. METHOD.: Prospective study of consecutive cases of ovarian cancer undergoing primary surgical treatment at the Gynecologic Oncologic Center after the introduction of centralised primary surgery. Results of treatment recorded up to the date of last examination or death.

RESULTS.: From 1999 to 2002, 107 patients with primary epithelial ovarian cancer underwent primary surgery at the Gynecologic Oncologic Center, Aalborg. This corresponds to 95.5% of patients with invasive carcinoma in the County of North Jutland. All patients with Stage I to Stage IIIB disease had a complete, macroscopically radical cytoreduction performed. In patients with Stage III and IV invasive tumors, the optimal debulking rate was 79.5%, and, in Stage IIIC and IV, the optimal debulking rate was 78.2%. Intra-operative and post-operative complications were generally few. Post-operative death, defined as death within 30 days after surgery, was observed in 4 cases (3.7%). After primary surgery, platinum-based chemotherapy was given in most cases. For Stage I to IV invasive cancer, the median survival was 46 months. In patients with Stage IIIC and IV disease, the median survival was 32 months. In optimally debulked Stage IIIC and IV disease, the median survival was 41 months.

CONCLUSIONS.: The results indicate a survival benefit after introduction of centralised primary surgery. Compared to existing national and regional data on survival in ovarian cancer, the results indicate an increase in median survival for all stages of approximately 15 months. Centralisation of primary surgery to centres with the necessary expertise may be the most significant way to increase survival in ovarian cancer in Denmark

Genetic predisposition is reason to screen, new guidelines say

This article unfortunately misses other familial cancer risks such as colorectal and uterine cancers in the family.
Sandi

Genetic predisposition is reason to screen, new guidelines say

By Rita Rubin, USA TODAY
September 5th, 2005

Doctors should refer only those women whose family history suggests that they might be susceptible to breast or ovarian cancer for genetic counseling and testing, say guidelines out today from an independent, government-sponsored panel.

About one in 50 U.S. women have such a family history, according to the U.S. Preventive Services Task Force's new recommendations on testing for mutations in BRCA1 or BRCA2 — so-called breast cancer genes that also raise ovarian cancer risk.

'Breast cancer genes' and family history Family history is associated with an increased risk of mutations in the so-called breast cancer genes, according to a government task force. For women who are of Ashkenazi descent: Two or more second-degree relatives on the same side of the family diagnosed with breast or ovarian cancer at any age. One first-degree relative diagnosed with breast or ovarian cancer at any age. For women who are not of Ashkenazi (Eastern European Jewish) descent: Two first-degree relatives (mother, sister, daughter) with breast cancer, at least one of whom was diagnosed before age 50. Three or more first- or second-degree (grandparent, aunt, cousin) relatives diagnosed with breast cancer at any age. A first-degree relative with cancer in both breasts diagnosed at any age. Two or more first- or second-degree relatives diagnosed with ovarian cancer at any age. A male relative with breast cancer.

This is the task force's first set of guidelines on genetic testing.

The panel focused on BRCA testing because, although the technology has been widely available for a number of years, "there was confusion on the part of providers (doctors) and patients about who should get the test," says panel chair Bruce Calonge, chief medical officer of the Colorado Department of Public Health and Environment.

The confusion stems partly from how the test has been marketed to doctors and genetics counselors, Calonge says.

Only a minority of women whose family history indicates they may be susceptible have actually inherited a BRCA mutation, and not all of them will develop cancer, according to the panel.

In women with such a mutation, the risk of developing breast cancer by age 70 is estimated to be 35% to 84% for breast cancer, 10% to 50% for ovarian cancer.

If a BRCA mutation is found, studies show that women can greatly reduce their cancer risk by having their breasts or ovaries removed, the task force writes in the Annals of Internal Medicine.

But evidence is lacking about whether aggressive screening, including MRI, or drugs that reduce breast cancer risk, such as tamoxifen, actually reduce the chances of dying from breast cancer in women with BRCA mutations.

Further research into screening and managing women at high risk for ovarian cancer is also needed, the task force says.

Routinely referring women who do not have an increased-risk family history for genetic counseling and, possibly, testing "clearly has important psychological, ethical and social implications," although those have not been well described by researchers, according to the panel.

Barbara Brenner, executive director of Breast Cancer Action in San Francisco, says, "This set of recommendations, which looks at all the research that's available, says what we've been saying for a long time: The marketing of genetic testing is far too broad."

In an accompanying editorial, Wylie Burke, a University of Washington School of Medicine ethicist, writes that implementing the new guidelines "would require a concerted effort to change current practice."

Taking a family history has long been considered an important part of a medical evaluation, but few doctors gather the detailed information required by the guidelines, Burke writes.

2005 Aug: Gynecol Oncol. 2005 Aug 30; Clinical and pathologic findings of prophylactic salpingo-oophorectomies in 159 BRCA1 and BRCA2 carriers.

Clinical and pathologic findings of prophylactic salpingo-oophorectomies in 159
BRCA1 and BRCA2 carriers.
Gynecol Oncol 2005 Aug 30 PMID: 16137750

Finch A, Shaw P, Rosen B, Murphy J, Narod SA, Colgan TJ
The Centre for Research in Women's Health, 790 Bay Street, 7th Floor, Toronto, ON, Canada M5G 1N8; The Familial Ovarian Cancer Clinic, Princess Margaret Hospital, University Health Network, Canada.

OBJECTIVE.: To estimate the likelihood of occult cancer diagnosis at prophylactic oophorectomy in BRCA1 and BRCA2 carriers in different age groups and to determine the histopathology of these lesions. METHODS.: We describe a series of 159 female BRCA1 or BRCA2 carriers who underwent prophylactic oophorectomy at the University Health Network, Toronto from January 1, 1992 to June 30, 2004.

RESULTS.: Seven (4.4%) occult cancers were detected at pathologic examination. None of the 159 subjects had clinical signs or symptoms of ovarian carcinoma prior to, or at the time of, surgery. Only two cancers were grossly visible at surgery. There were 94 BRCA1 carriers, of whom six were found to have an occult cancer (6.4%). In contrast, only one of the 65 BRCA2 carriers was found to have an occult cancer (1.5%). Three of the seven cases of occult malignancy involved the fallopian tube and not the ovaries.

CONCLUSION.: Approximately 6% of BRCA1 carriers and 2% of BRCA2 carriers who undergo prophylactic salpingo-oophorectomy will be found to have occult carcinomas if the ovaries and tubes are rigorously examined. A significant proportion of these appear to originate in the fallopian tube. No cancers were detected among women who had the operation at age 39 or younger.

2005 Erythropoietin Use in Cancer Patients: A Matter of

Erythropoietin Use in Cancer Patients: A Matter of
Life and Death?

2005 EDITORIALS: It is Time to Get Serious About Diagnosing Lynch Syndrome

"Although patient-reported family cancer histories appear
to be accurate and valuable for colorectal cancer risk
assessments, nearly one half of oncologists fail to document
a comprehensive family history, and among those
that do, few take appropriate action if it is positive with
respect to referral for genetic evaluation."

Hereditary nonpolyposis colorectal cancer (HNPCC),
also called Lynch syndrome after Henry T. Lynch,
MD, a pioneer in the field, is an autosomal dominant
hereditary cancer syndrome, which accounts for upwards
of 3% of all colorectal cancers and is associated with
an increased risk of endometrial, ovarian, and other extracolonic
cancers. Colorectal cancer can be averted in
Lynch syndrome by early an intensive surveillance, and
has been shown to be cost-effective. The syndrome
originally was defined in clinical terms by the stringent
Amsterdam criteria, although over time more relaxed
clinical definitions have been suggested, culminating in
the recently published revised Bethesda guidelines.

New York Times/Aug 16th, 2005: In the Hospital, a Degrading Shift From Person to Patient

Stop being a good girl, she says; you've got a mouth; you should use it. Have someone with you at all meetings with doctors, if possible. And take notes.

"Otherwise," she said, "you cease being a person and become 'the carcinoma in Room B-2,' like I was."

August 2005: Who should operate on Ovarian Cancer?

ARTICLE IN PRESS
Review
Who should operate on patients with ovarian cancer?
An evidence-based review

Kurt Christopher Giede*, Katharina Kieser, Jason Dodge, Barry Rosen
University of Toronto, Canada
Received 5 June 2005

Abstract
Objective. To evaluate the relationship between surgical specialty and survival in patients receiving initial surgical management for
ovarian epithelial cancer.

Study methods. An analytic framework was constructed to address the principle question Fdoes the type of surgeon operating on patients
with newly diagnosed ovarian epithelial cancer influence survival?_ A literature search addressing the components of this analytic framework
was carried out using the Cochrane Library, Medline, EMBASE, and HealthSTAR databases. Relevant articles were selected and graded
using U.S. Preventive Services Task Force and Canadian Task Force guidelines. Results were summarized by quality as well as level of
evidence.

Results. Eighteen studies were reviewed. The quality of evidence was good in 3, fair in 8, and poor in 7 of the studies. The most common
study flaws encountered were Ffailure to account for confounders_ and Fincompleteness of data_. In studies focusing on advanced disease,
there was good quality evidence to support a 6- to 9-month median survival benefit for patients operated on by gynecologic oncologists rather
than general gynecologists and/or general surgeons ( P values 0.009 to 0.01). Studies focusing on early stage disease found gynecologic
oncologists more likely to carry out optimal staging ( P values 0.001 to 0.01). Increased survival could be explained by improved
identification of true stage I patients.

Conclusion. Patients receiving initial surgical management for ovarian epithelial cancer should be operated on by gynecologic
oncologists.


Gynecologic Oncology xx (2005) xxx – xxx
www.elsevier.com/locate/ygyno
YGYNO-971157; No. of pages: 15; 4C:
DTD 5
ARTICLE IN PRESS

Introduction

In the past two decades, there has been increasing interest
in the relationship between surgical specialty and outcomes
in cancer treatment [1].
Surgical specialty has been shown to have a positive
influence on outcomes in a variety of cancers [1–6]. In
ovarian cancer, a relationship between sub-specialty training
and survival has been suggested [1].
Although recommendations and guidelines on the
management of ovarian cancer exist [7–13], to date, there
have been no thorough evidence-based reviews specifically
addressing the question Fdoes the type of surgeon operating
on patients with newly diagnosed ovarian epithelial cancer
influence long-term survival?_
The following review was conducted not only to examine
the quantity but also the quality of evidence regarding a
possible relationship between surgical specialty and survival
outcomes in ovarian cancer.

Methods
Our review followed the methodology established by
the 2001 U.S. Preventive Services Task Force (USPSTF)
and Canadian Task Force (CTF) guidelines [14,15]. An
analytic framework was constructed in order to better
understand the influence of surgical specialty on survival
in patients with newly diagnosed ovarian epithelial cancer
(Appendix Fig. 1). This framework was built around the
principle or Foverarching question_ Fdoes surgical specialty
influence survival in patients being operated on for newly
diagnosed ovarian epithelial cancer?_ The population of
interest was women with newly diagnosed ovarian
epithelial cancer in whom initial management was
surgical. The intervention of interest was the type of
surgeons operating on patients and included general
surgeons (GS), general gynecologists (GYN), and gynecologic
oncologists (GO). The principle outcomes of interest
were median and 5-year overall survival. Additional
outcomes important to the analysis included degree of
cytoreduction and proportion of patients with optimal
cytoreduction.
To facilitate the stage-dependent surgical approach to
ovarian cancer, the analytic framework was divided into two
parts: part 1 representing patients with advanced disease
requiring cytoreduction and part 2 representing patients with
early disease requiring accurate staging.
The goal of Part I of the framework was to address the
question Fdo patients with advanced stage ovarian epithelial
cancer who receive upfront surgical debulking have
different survival rates when operated on by GO, GYN, or
GS?_ The analytic framework for Part 1 also examined the
link between patients and survival by addressing two
questions:

1. Is the proportion of patients with optimal cytoreduction
influenced by surgical specialty? (Link 1)
2. Do patients who have optimal cytoreduction have an
improved survival? (Link 2)
The goal of Part II of the framework was to address
the question Fdo patients with early stage disease have
different survival when operated on by GO, GYN, or
GS?_
This part of the analysis also looked at a potential link
between patients with early stage disease and improved
survival by addressing the following questions:
1. Is the proportion of patients who receive complete or
comprehensive staging surgery influenced by surgical
specialty? (Link 1)
2. Do patients who have full staging surgery have an
improved survival? (Link 2)
The final component in each part of the framework
addressed potential adverse effects of exposure to different
types of surgeons.
Inclusion/exclusion criteria were set up to identify
articles pertinent to those components of the analytic
K.C. Giede et al. / Gynecologic Oncology xx (2005) 2 xxx –xxx


Results
Literature search
No evidence-based guidelines linking surgical specialty
with ovarian cancer outcomes were found within the
Cochrane database. The Medline search revealed 109
potential articles, of which 33 abstracts were selected for
review. Two additional abstracts were found when the
search was repeated in EMBASE, but no additional
abstracts were found in HealthSTAR.
From these 35 abstracts, 15 met the inclusion criteria for
review. Cross-referencing of existing reviews provided 3
additional studies for review. Thus, a total of 18 articles met
the inclusion criteria for review.


Discussion
The past three decades have brought advances in both the
medical and surgical management of ovarian epithelial
cancer [41]. Unfortunately, these advances have had little
impact on long-term survival [42], leaving ovarian cancer as
the leading cause of gynecologic cancer related mortality in
North America [43]. It is therefore imperative that we
understand where inroads have been made in order that we
maximize patient access to those treatments responsible for
improving outcome.

At the beginning of the 20th century, women with
ovarian cancer were operated on primarily by general
surgeons and general gynecologists [45]. It was not until
1970 that subspecialty training in gynecologic oncology was
established in the United States [46]. Such training has been
introduced even later to Europe [45,23,24]. Our review of
the relationship between surgical specialty and survival
outcome covers this transition period. In fact, several of the
studies we reviewed looked at the regional impact of
changing policies regarding the management of ovarian
cancer [23,24,26].

Guidelines and recommendations on managing patients
with ovarian cancer do exist. Although strongly advocating
that patients be treated by gynecologic oncologists, the
majority of these guidelines are not evidence-based
[12,13].

Evidence-based guidelines on the management of
patients with adnexal masses have recently been put forth
by the Society of Gynecology and Obstetrics of Canada [8].
In these guidelines, it has been recommended that all
patients with ovarian cancer have access to comprehensive
staging and optimal cytoreductive surgery. Unfortunately,
this review does not access who should perform that surgery
nor does it comment on the Fquality of evidence_ leading to
those recommendations.
We used the most recent USPSTF and CTF guidelines on
evidence-based reviews to access the internal validity of
each study reviewed [14,15]. Using this system allowed us
to make recommendations based on good quality of
evidence.
With this approach, we found good quality of evidence
demonstrating a 6- to 9-month median survival benefit for
patients operated on by gynecologic oncologists (P values
0.009 to 0.01) [23,32]. There was also good quality
evidence that the proportion of patients receiving optimal
cytoreductive surgery was significantly increased in patients
operated on by gynecologic oncologists [23,32]. Although
we did not conduct a full review of the link between
survival and degree of cytoreduction, we felt that existing
meta-analyses of this topic demonstrated that patient
populations with increased rates of optimal cytoreduction
had improved median survival rates [35,46].
For patients with early stage disease, we found good
quality of evidence to support a decreased recurrence rate
in patients receiving comprehensive staging [26]. There
was also fair quality evidence to support a 24% improved
survival rate in patients receiving comprehensive staging
by a gynecologic oncologist [27]. Furthermore, fair
quality of evidence demonstrated that gynecologic oncologists
were more likely to carry out comprehensive
staging [28].

We did not find evidence that comprehensive surgery
itself improves patient survival. Nevertheless, good data
from randomized trials clearly demonstrate the benefit of
full staging surgery [38,39]. Decreased recurrence rates and
subsequent improved survival are in large due to the ability
of comprehensive surgery to separate those patients with
true stage I disease from those with microscopic stage III
disease. It is the latter patient who benefits the most from
adjuvant chemotherapy.


Limitations
There were several limitations to our review. First, the
degree of heterogeneity among the patient populations,
surgical interventions, and reported outcomes made it
untenable to conduct a meta-analysis of the reported results.
Second, all the studies reviewed represented level II-b
evidence. However, well-designed cohort studies may be of
more value then poorly designed randomized studies [14].
That the majority of studies reviewed were conducted
by gynecologic oncologists could have led to self-interest
and publishing bias. However, the demonstration that
general gynecologists achieving higher rates of optimal
cytoreduction also had improved survival rates supports a
biological explanation for improved outcomes. Thirdly, our
review did not address the use of neoadjuvant chemo-
K.C. Giede et al. / Gynecologic Oncology xx (2005) xxx– xxx 7


Finally, the mere existence of guidelines does not
guarantee their application. Munoz et al. (1997) provided
a good review of patterns of care for women with ovarian
cancer in the United States [47], demonstrating that, even
with the existence of guidelines, only 10% of patients with
early stage disease, 71% of patients with stage III disease,
and 53% with stage IV disease received recommended
management. It is our hope that, with increasing emphasis
on evidence-based guidelines and increased physician
awareness of recommendations, these practices will change
for the better.

Conclusion

There is good level II-2 evidence demonstrating the
following:
1. Patients with advanced disease operated on by gynecologic
oncologists are more likely to receive optimal
cytoreductive surgery.
2. Patients with advanced disease operated on by gynecologic
oncologists have an improved median and overall
5-year survival.
3. Patients with advanced disease operated on by general
gynecologists can have survival equal to patients
operated on by gynecologic oncologists if rates of
cytoreduction are equal.
4. Patients with early stage disease are more likely to have
comprehensive staging when operated on by gynecologic
oncologists, allowing for better selection of patients
requiring adjuvant chemotherapy.

We conclude that patients with both advanced and early
stage ovarian epithelial cancer should be operated on by
specialists trained in Gynecological Oncology (level A and
level B recommendations based on good level II-2
evidence).

Management of HNPCC (Lynch Syndrome) cancer patients as per Myriad Labs

Please note: there are no standard practice guidelines for the managment of Lynch syndrome patients and the followup of these patients may vary depending on your location/healthcare institution. In addition, family history is still the most important criteria irrespective of a negative test result. Sandi
Following a positive test result, preventive measures such as these can be taken. This type of ongoing surveillance may lead to early detection and intervention which may, in turn, positively impact outcomes for HNPCC patients. Increased Surveillance for Colorectal Cancer Colonoscopy every one to two years beginning at age 20-25 or 5-10 years before the earliest age of a diagnosed colorectal cancer in patient's family, whichever comes first. Colonoscopy annually after age 40.24, 52, 53 Surgical Management for Colorectal Cancer If colon cancer is diagnosed (or if more than one advanced adenoma is found) in a patient with HNPCC, total colectomy with ileorectal anastomosis OR hemicolectomy are the recommended surgical procedures, rather than segmental colectomy.54 In carefully selected patients, (i.e. those not willing or able to undergo periodic screening) prophylactic total colectomy with ileorectal anastomosis may be presented as an option based on carrier status alone.24, 54 Increased Surveillance for Endometrial Cancer Gynecologic exam, transvaginal ultrasound, endometrial aspiration, and CA-125 every one to two years, beginning at age 25-35.24, 52 Surgical Management for Endometrial and Ovarian Cancer Prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy may be considered if colorectal cancer is detected and may also be considered as an option when childbearing is concluded (especially if bleeding or other symptoms of uterine or ovarian disease occur).24, 54 Increased Surveillance for Other HNPCC-Related Cancers The following screening may be recommended based on the patient's family history.21, 24 For stomach cancer, gastroscopy every one to two years starting at age 30-35. For urinary tract cancer, ultrasonography or urine cytology every one to two years starting at age 30-35.

HNPCC cancer risks (updated 2005) - now known as the Lynch Syndrome

People with an HNPCC gene mutation have greater than a 90 percent lifetime risk of developing some type of cancer.28 These individuals not only have an increased risk of colorectal and endometrial cancers, but also other cancers listed below: Cancer Type Mutation Carrier Risk1, 35 General Population Risk Colorectal Up to 82% 2% Endometrial Up to 71% 1.5% Stomach Up to 13% <1% Ovarian Up to 12% 1% * Patients with HNPCC may also have a slightly elevated risk of the following cancers when compared to the general population: ureter/renal pelvis, biliary tract, small bowel, pancreas, brain and sebaceous adenomas. Individuals with HNPCC who have already been diagnosed with cancer also have an increased risk of developing a second cancer. In these patients, there is a 30 percent risk of a second cancer developing within 10 years of initial diagnosis and a 50 percent chance of a second cancer developing within 15 years of initial diagnosis.

2005 August: Hormone replacement therapy and the risk of ovarian cancer in BRCA 1/2 mutation carriers

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16137751
Gynecol Oncol. 2005 Aug 30

Hormone replacement therapy and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.

Kotsopoulos J, Lubinski J, Neuhausen SL, Lynch HT, Rosen B, Ainsworth P, Moller P, Ghadirian P, Isaacs C, Karlan B, Sun P, Narod SA.
Centre for Research in Women's Health, 790 Bay Street, 7th Floor, Women's College Hospital, University of Toronto, Toronto, Ontario, Canada M5G 1N8; Department of Nutritional Sciences, University of Toronto, Ontario, Canada.

OBJECTIVE.: Hormone replacement therapy (HRT) is commonly prescribed to alleviate the climacteric symptoms of menopause. Recent findings from the Women's Health Initiative has raised questions about the routine use of HRT due to the increased observed incidence of cardiovascular disease and of breast and ovarian cancers in the treatment arm of the trial. In the general population, the association between HRT use and risk of ovarian cancer has not yet been resolved. This association has not been evaluated in BRCA1 or BRCA2 mutation carriers who face very high lifetime risks of both breast and ovarian cancers.

METHODS.: We conducted a matched case-control study on 162 matched sets of women who carry a deleterious mutation in either the BRCA1 or BRCA2 gene. Women who had been diagnosed with ovarian cancer were matched to control subjects by mutation, year of birth, and age at menopause. Information on HRT use was derived from a questionnaire routinely administered to women who were found to be carriers of a mutation in either gene. Conditional logistic regression was used to estimate the association between HRT use and the risk of ovarian cancer, stratified by mutation status and type of HRT.

RESULTS.: Compared with those who had never used HRT, the odds ratio associated with ever use of HRT was 0.93 (95% CI = 0.56-1.56). There was no significant relationship with increasing duration of HRT use. There was a suggestion that progestin-based HRT regimens might protect against ovarian cancer (odds ratio = 0.57) but this association was not statistically significant (P = 0.20). CONCLUSION.: HRT use does not appear to adversely influence the risk of ovarian cancer in BRCA mutation carriers.

2005 September: Hormone Replacement therapy after cancers

http://makeashorterlink.com/?K51452CBB
ARTICLE LINKS:

Hormone replacement therapy after cancers.
Current Opinion in Oncology. 17(5):493-499, September 2005.
Creasman, William T

Abstract:

Purpose of review: The role of female hormones in estrogen-dependent cancers has been debated for years. This is particularly true of breast cancer. Retrospective, case, and cohort control studies usually have suggested no influence.

The Women's Health Initiative study in 2002, a prospective double-blind study, noted an increased risk of breast cancer if estrogen plus progesterone was given.

In the estrogen-only arm of that study, a decreased (not significant) risk of breast cancer was noted. With this controversy, can estrogen be given safely to a woman who has been treated for breast cancer? The relation between endometrial cancer and unopposed estrogen is well established. With clear-cut evidence of this relation, is there evidence to suggest a role for replacement therapy in women who have been treated for endometrial cancer?

Recent findings: Several case-control and cohort studies have noted either no increased risk or actually less risk of recurrence in women taking estrogen after therapy after breast cancer. Although the general consensus is that such a recommendation is contraindicated, the data do not support this admonition. The current data suggest that replacement therapy can be given to the woman who has been treated for endometrial cancer.

Summary: There seems to be little if any risk in giving hormone replacement therapy to women who have had breast or endometrial cancer. There are no data to suggest that hormone replacement therapy is contraindicated in women who have been treated for cervical or ovarian cancer.