Sunday, September 11, 2005
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
Tuesday, September 06, 2005
This article unfortunately misses other familial cancer risks such as colorectal and uterine cancers in the family.
Genetic predisposition is reason to screen, new guidelines say
September 5th, 2005
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.
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.
Erythropoietin Use in Cancer Patients: A Matter of
Life and Death?
Monday, September 05, 2005
"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.
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."
ARTICLE IN PRESS
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
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
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
Gynecologic Oncology xx (2005) xxx – xxx
YGYNO-971157; No. of pages: 15; 4C:
ARTICLE IN PRESS
In the past two decades, there has been increasing interest
in the relationship between surgical specialty and outcomes
in cancer treatment .
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 .
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.
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
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
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
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
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.
The past three decades have brought advances in both the
medical and surgical management of ovarian epithelial
cancer . Unfortunately, these advances have had little
impact on long-term survival , leaving ovarian cancer as
the leading cause of gynecologic cancer related mortality in
North America . It is therefore imperative that we
understand where inroads have been made in order that we
maximize patient access to those treatments responsible for
At the beginning of the 20th century, women with
ovarian cancer were operated on primarily by general
surgeons and general gynecologists . It was not until
1970 that subspecialty training in gynecologic oncology was
established in the United States . 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
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
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 .
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
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
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 . There
was also fair quality evidence to support a 24% improved
survival rate in patients receiving comprehensive staging
by a gynecologic oncologist . Furthermore, fair
quality of evidence demonstrated that gynecologic oncologists
were more likely to carry out comprehensive
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
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 .
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 , 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.
ConclusionThere is good level II-2 evidence demonstrating the
1. Patients with advanced disease operated on by gynecologic
oncologists are more likely to receive optimal
2. Patients with advanced disease operated on by gynecologic
oncologists have an improved median and overall
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
|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. |
2005 August: Hormone replacement therapy and the risk of ovarian cancer in BRCA 1/2 mutation carriers
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.
Hormone replacement therapy after cancers.
Current Opinion in Oncology. 17(5):493-499, September 2005.
Creasman, William T
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.
Tuesday, August 30, 2005
I am a good patient, believe it or notAlejandro R Jadad, Carlos A Rizo and Murray W Enkin
What service might “good patients” of the future expect from their dcotors? We asked a team of clinicians for their views.
The good patient of the future will:
■ Bring lists of questions to theWhat Patients Want from their Doctors:
consultation and will expect answers
in clear terms
■ Know how involved they want to
be in decisions about their health
care; most will choose to share
decisions with their healthcare
■ Have free access to their health
record on paper or through
electronic means and will use it or
share it as they see fit
■ Request and receive a second
opinion whenever they face a major
diagnosis or decisions about
■ Use telephone, internet, and other
forms of communication to
complement personal visits with
members of the healthcare team
Patients want many
things from their doctors,
not all of which are
possible. Mike Stone,
director of the UK’s
Patients Association, lists
what he believes patients
want from their doctors.
■ Eye contact
There is nothing worse
than walking into a
consulting room and
not getting any eye
contact from the
doctor. It happened to
me only last week. I
knocked on the door to
be greeted with
“Come” and to find the
doctor sitting looking
at his computer screen.
He continued to do so
while asking why I had
come to see him.
Patients want to be
people who doctors do
things with, not people
that doctors do things
to. Patients want to be
consulted about their
treatment, and how
things will progress
from the consultation.
doctor to patient and
vice versa is the key to
patients still feel that
they are entering “alien
territory” when they go
to see their doctor. In
many cases they are
scared, they don’t
understand what the
doctor is saying, and
they are not able to
take everything in that
they are told. Just as
doctors may have
a patient’s explanation
of symptoms, so
patients may have
a doctor’s explanation
of the diagnosis.
Patients want to spend
more time with their
doctor: they want time
to be able to explain
things and have things
explained to them. We
all know that there is a
shortage of doctors,
and we know that a
doctor’s time is
valuable. However, if
one wish could be
granted for patients it
would be for more time
with their doctor.
Patients want to get to
see their doctor within
a reasonable time; not
weeks, but rather a few
days, or, in the case of
a person who is unwell,
a few hours if possible.
Saturday, August 27, 2005
Promotion of mammary cancer development by tamoxifen in a mouse model of Brca1-mutation-related breast cancer
Oncogene (2005) 24, 3554−3562. doi: 10.1038/sj.onc.1208426 Published online 7 March 2005
Published online 07 March 2005
Promotion of mammary cancer development by tamoxifen in a mouse model of Brca1-mutation-related breast cancer
Laundette P Jones1, Minglin Li1, Ewa D Halama1, Yongxian Ma1, Ronald Lubet2, Clinton J Grubbs3, Chu-Xia Deng4, Eliot M Rosen1 and Priscilla A Furth1
1. 1Department of Oncology, Lombardi Cancer Center, Georgetown University, Washington, DC 20057, USA
2. 2National Cancer Institute, Division of Chemoprevention, Bethesda, MD, USA
3. 3Chemoprevention Center, University of Alabama at Birmingham, Birmingham, AL, USA
4. 4National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Correspondence: PA Furth, Georgetown University, Research Building Room E520A, 3970 Reservoir Road, Washington, DC 20057, USA
Received 20 July 2004; Revised 01 November 2004; Accepted 01 December 2004; Published online 07 March 2005.
Loss of full-length Brca1 in mammary epithelial cells of the mouse mammary tumor virus (MMTV)-Cre Brca1 conditional exon 11 deletion mouse model results in the development of mammary adenocarcinomas with similar genetic changes to those found in human BRCA1-mutation-related breast cancers. We used this experimental model to evaluate the chemopreventive effect of tamoxifen on the development of mammary preneoplasia and adenocarcinoma. No protective effects of tamoxifen administration on mammary cancer development were found. Instead, tamoxifen treatment significantly increased rates of mammary epithelial cell proliferation and the prevalence of mammary hyperplasia at 6 months of age. Tamoxifen-exposed mice developed adenocarcinomas at younger ages than control mice and a higher percentage of mice developed adenocarcinomas by 12 months of age. Both whole mouse and tissue culture cell models were used to test if loss of full-length Brca1 was associated with a relative increase in the agonist activity of tamoxifen. Tamoxifen induced increased ductal growth in MMTV-Cre Brca1 conditional mice compared to wild type. Estrogen receptor alpha (ERalpha) expression was downregulated in the tamoxifen-induced hyperplasias. Reducing BRCA1 levels in MCF-7 cells using siRNA resulted in a relative increase in the agonist activity of tamoxifen. Results suggest a model of mammary cancer progression in which loss of full-length Brca1 altered the agonist/antagonist activity of tamoxifen, resulting in tamoxifen-induced mammary epithelial cell proliferation with subsequent loss of ERalpha expression and development of ERalpha-negative hyperplasias and adenocarcinomas.
GeneticHealth websiteby sandipniauskas @ 2005-08-17 - 05:12:59 pm
2001 JAMA: Tamoxifen and Breast Cancer Incidence Among Women With Inherited Mutations in BRCA1 and BRCA2by sandipniauskas @ 2005-08-17 - 05:10:51 pm
Tamoxifen and Breast Cancer Incidence Among Women With Inherited Mutations in BRCA1 and BRCA2
National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial
Mary-Claire King, PhD; Sam Wieand, PhD; Kathryn Hale, BS; Ming Lee, PhD; Tom Walsh, PhD; Kelly Owens, PhD; Jonathan Tait, MD, PhD; Leslie Ford, MD; Barbara K. Dunn, MD, PhD; Joseph Costantino, DrPH; Lawrence Wickerham, MD; Norman Wolmark, MD; Bernard Fisher, MD
Context Among cancer-free women aged 35 years or older, tamoxifen reduced the incidence of estrogen receptor (ER)–positive but not ER-negative breast cancer. The effect of tamoxifen on breast cancer incidence among women at extremely high risk due to inherited BRCA1 or BRCA2 mutations is unknown.
Objective To evaluate the effect of tamoxifen on incidence of breast cancer among cancer-free women with inherited BRCA1 or BRCA2 mutations.
Design, Setting, and Participants Genomic analysis of BRCA1 and BRCA2 for 288 women who developed breast cancer after entry into the randomized, double-blind Breast Cancer Prevention Trial of the National Surgical Adjuvant Breast and Bowel Project (between April 1, 1992, and September 30, 1999).
Main Outcome Measure Among women with BRCA1 or BRCA2 mutations, incidence of breast cancer among those who were receiving tamoxifen vs incidence of breast cancer among those receiving placebo.
Results Of the 288 breast cancer cases, 19 (6.6%) inherited disease-predisposing BRCA1 or BRCA2 mutations. Of 8 patients with BRCA1 mutations, 5 received tamoxifen and 3 received placebo (risk ratio, 1.67; 95% confidence interval, 0.32-10.70). Of 11 patients with BRCA2 mutations, 3 received tamoxifen and 8 received placebo (risk ratio, 0.38; 95% confidence interval, 0.06-1.56). From 10 studies, including this one, 83% of BRCA1 breast tumors were ER-negative, whereas 76% of BRCA2 breast tumors were ER-positive.
Conclusion Tamoxifen reduced breast cancer incidence among healthy BRCA2 carriers by 62%, similar to the reduction in incidence of ER-positive breast cancer among all women in the Breast Cancer Prevention Trial. In contrast, tamoxifen use beginning at age 35 years or older did not reduce breast cancer incidence among healthy women with inherited BRCA1 mutations. Whether tamoxifen use at a younger age would reduce breast cancer incidence among healthy women with BRCA1 mutations remains unknown.
Author Affiliations: Departments and Medicine and Genomic Sciences (Drs King, Lee, Walsh, and Owens and Ms Hale) and Laboratory Medicine (Dr Tait), University of Washington, Seattle; and National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh, Pittsburgh, Pa (Drs Wieand, Costantino, Wickerham, Wolmark, and Fisher); and National Cancer Institute, Bethesda, Md (Drs Ford and Dunn).
2001 study: Findings on Tamoxifen for BRCA-1 and 2 Mutation Carriersby sandipniauskas @ 2005-08-17 - 05:05:55 pm
2005 Brain metastases from epithelial ovarian cancer. The Hellenic Cooperative Oncology Group (HeCOG) experience and review of the literature.by sandipniauskas @ 2005-08-17 - 03:10:39 pm
Anticancer Res. 2005 Sep-Oct;25(5):3553-8.
Brain metastases from epithelial ovarian cancer. The Hellenic Cooperative Oncology Group (HeCOG) experience and review of the literature.
Pectasides D, Aravantinos G, Fountzilas G, Kalofonos C, Efstathiou E, Karina M, Pavlidis N, Farmakis D, Economopoulos T, Dimopoulos MA.
Second Department of Internal Medicine-Propaedeutic, Oncology Section, University General Hospital Attikon, Haidari, Athens, Greece.
BACKGROUND: Brain metastases from epithelial ovarian cancer (EOC) are rare. A retrospective study of all patients diagnosed with brain metastases from EOC over the last 20 years, according to the Hellenic Cooperative Oncology Group (HeCOG) tumor registry, was conducted.
PATIENTS AND METHODS: A total of 1450 patients with EOC were treated within various HeCOG protocols from 1983 to 2004. Seventeen (1.17%) of them developed brain metastases.
RESULTS: The median age at diagnosis of brain metastases was 58 years (range, 24 to 77). At initial diagnosis, 2 patients had stage II, 12 had stage III and 3 had stage IV disease. Serous papillary adenocarcinoma was the most common histological subtype [12 patients (71%)]. All patients had received initial cisplatin-based chemotherapy. The median time from initial diagnosis to central nervous system (CNS) relapse was 15.9 months (range, 1.4 to 70.8). The CNS was the only site of disease in 13 (76.5%) patients, whereas 4 (23.5%) patients had additional extracranial disease. Two (12%) patients with isolated single brain lesions underwent surgical excision of the metastases, followed by whole brain radiation therapy (WBRT) and chemotherapy. Four (24%) patients were treated with WBRT alone, 6 (35%) patients with WBRT plus chemotherapy and 2 (12%) had only supportive care, while 3 (18%) patients decided not to have any further treatment after the diagnosis of brain metastases. The median survival time from diagnosis of CNS relapse was 5.7 months (range, 0.2 to 22.6) and the median survival time from diagnosis of EOC was 27.4 months (range, 3.0 to 71.4). In patients with CNS recurrence as the only site of disease, the median survival time from diagnosis of CNS relapse was 5.3 months (range, 0.6 to 22.6) and in those with both CNS and extracranial disease, the median survival time was 3.9 months (range, 0.2 to 11.9) (p=0.5597). There was a statistically significant difference in survival for those treated with WBRT plus chemotherapy (10.0 months) versus those treated with WBRT alone (1.5 months) and those who had only supportive care (0.2 months) (p=0.0003).
CONCLUSION: The incidence of cerebral metastases in our patients with EOC was 1.17%, which is consistent with the mean value of all series reported in the literature. The prognosis of patients with brain metastases from EOC is poor. Patients who had WBRT and chemotherapy fared better than those who received WBRT alone.
2005 It Is Time to Get Serious About Diagnosing Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancerby sandipniauskas @ 2005-08-17 - 02:40:29 pm
It Is Time to Get Serious About Diagnosing Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer With Defective DNA Mismatch Repair) in the General Population
Doctors and Patients - Working Together to Make Medical Decisionsby sandipniauskas @ 2005-08-17 - 02:35:12 pm
Dr. Margaret Spitz
Doctors and Patients - Working Together to Make Medical Decisions
Several articles in the recent literature have suggested interesting patterns in health care decisions among groups of patients. One article describes how race and marital status were linked to the decisions a group of men diagnosed with localized prostate cancer made regarding the type of therapy to pursue - black and single men tended to choose radiation therapy, while white and married men tended to choose surgery. Another study shows that among women with locally advanced breast cancer, emotional, religious, and marital factors delayed their pursuit of treatment after diagnosis. It seems that many factors can influence patients' decisions about cancer treatment, not simply the advice of their physicians.
Doctors and Patients Working Together"We've generally assumed people will always make rational decisions when it comes to their health," explains Dr. Wendy Nelson of NCI's Basic and Biobehavioral Research Branch, "but as human beings, our decisions are often guided by intuition and emotion, rather than fact and reason."
Dr. Nelson leads a scientific initiative at NCI that promotes research on the cognitive and affective processes underlying decision making in cancer control - for example, reasons why some people delay treatment that they know is in their best interest. Much of the research that was discussed at the initiative's first meeting, held in February of 2004, is published in a supplement to this month's issue of Health Psychology. Additionally, two program announcements, "Decision Making in Health: Behavior Maintenance" and "Decision Making in Cancer: Single-Event Decisions" were released by NCI at the end of last year to encourage more research in this area.
"Patients aren't computers, nor do they have the resources and time to always make these very difficult decisions," explains Dr. Nelson. "Often people rely on heuristics - rules of thumb that serve as automatic, intuitive guides to decision making - instead. But whenever you're dealing with medical uncertainty, there's no right or wrong answer. Through this initiative, we're trying to understand how people make decisions so health care providers can help patients make a truly informed decision that is consistent with their own values and preferences."
When a patient is facing a serious medical issue, the choices are never easy. In these situations, older adults tend to defer to their doctors for advice, a relationship known as the paternalistic decision-making model, while younger people tend to take a more active role in the decision. But regardless of the process, it's clear that the way in which information is presented to the patient makes a difference.
For example, if a surgeon says to a patient, "You will have a 90 percent chance of survival with this procedure," instead of saying, "There is a 10 percent chance of mortality," that can make a difference.
Sometimes too much information, or information overload, can also interfere with optimal decision making. Numbers and statistics can also interfere with decision making. Many people have difficulty understanding and interpreting numbers and are not accustomed to thinking in terms of probabilities, but they are often asked to make decisions based on probabilities.
What happens when a physician provides a patient with all of the information that he or she deems necessary to make a decision, but then feels the patient has made a wrong choice? In this case, who is ultimately responsible for what happens? The answer isn't always clear.
An article in last year's Journal of the American Medical Association illustrates this point well: In it, a doctor describes his experience providing the standard of care to a 53-year-old patient during a physical exam, including an overview of the risks and benefits of prostate cancer screening. The patient declined the test, but when another doctor later ordered the PSA test without discussing these options with the patient - subsequently diagnosing the man with advanced prostate cancer - a jury found the first doctor's residency program liable and awarded the man's family $1 million.
How, then, can physicians work with their patients to make these potentially life-altering decisions? "We know that just providing information is not enough," says Dr. Nelson. "Unless we understand how people are using and processing that information, we can't be sure that they're making a truly informed treatment choice."
A Service of the National Cancer Institute
Department of Health and Human Services National Institutes of Health FirstGov.gov
eMedicine - Borderline Ovarian Cancer : Article by Andrew E Green, MD - Last Updated: July 7, 2005by sandipniauskas @ 2005-08-17 - 02:26:30 pm
Last Updated: December 21, 2004 - Ovarian Cancer - Information on Ovarian Cancer Symptoms, Signs, Stages, and Treatment : Article by Agustin A Garcia, MDby sandipniauskas @ 2005-08-17 - 12:12:23 pm
legal news - Armstrong vs Centenaryby sandipniauskas @ 2005-06-20 - 06:44:57 am
Armstrong v. Centenary Health Centre
Citation : 2002 CanLII 42546 (ON S.C.) Date: December 20, 2002
Ontario > Superior Court of Justice
Citation : 2005 CanLII 20712 (ON C.A.) Date: June 13, 2005
Ontario > Court of Appeal for Ontario
July 3rd - "Ellie and Lisi Show" July 3rd, 2005 9:30 pm - 11:00 pm CFRB 1010 radio/on lineby sandipniauskas @ 2005-06-19 - 07:03:50 am
'The Ellie & Lisi Show'
CFRB - Sunday, July 3rd 9:30 pm -11:00 pm
Invited guest: Sandi Pniauskas
Ellie Tesher's life history has focused on social justice causes and issues, both in Canada and Internationally. Most recently, Ellie was honoured by the Jewish Women International of Canada's award (Toronto) as 'Woman of the Year'.
Both Ellie Tesher and her daughter, Lisi, are 'relationship' columnists. Their endeavours include columns in the print media, which are syndicated in Canada and the U.S.. As a Mother/Daughter team, they have come together to bring to you CFRB's highly successful one and a half-hour call-in show.
Sandi Pniauskas, a cancer survivour and patient advocate, will be Ellie's guest on CFRB's July 3rd program to discuss the many topics surrounding all manner of cancer concerns, hopes, desires, fears and information needs. Sandi's question to you is this: "Do you want to talk about cancer?"
Calls are THE key to the show's success and names are never required to ensure confidentiality. Ellie invites everyone to participate and looks forward to chatting with you. It's going to be a lively, informative chat! CFRB brings you this opportunity to have your voice heard. Call with your concerns and issues relating to cancer which affect you, whether you have/had a cancer diagnosis, family, friends or someone in the medical community who cares for cancer patients and their families.
There are several ways to access the program:
1) radio by tuning into CFRB 1010 AM (Toronto)
2) listen online: http://www.cfrb.com (click on show and guest information) or direct link
3) direct link: (http://tinyurl.com/bw37f) or
4) email comments/questions before Saturday, July 2nd: firstname.lastname@example.org
5) CALLS: 416-872-1010; 1-800-561-CFRB (toll free - Ontario only); and *TALK (8255) on a cellular