One Year Later


This note marks the one year anniversary since Ann received her breast cancer diagnosis and we'd like to take this opportunity to share two favorable bits of news with you.

First, the chemotherapy Ann chose is the most effective available at this time for early-stage breast cancer like her's. The second interim results from a phase III clinical trial conducted by the Breast Cancer International Research Group (BCIRG) were announced on Friday, December 5, at the San Antonio Breast Cancer Symposium (SABCS). The trial compares the efficacy of 5-FU versus Taxotere when administered along with Adriamycin and Cytoxan; these regimes go by the abbreviations FAC and TAC, respectively. (An article from the Wall Street Journal announcing the results appears below along with links to additional information that about the results available online.) We are very pleased to see that TAC, the regime that Ann chose, was the clear winner in both recurrence as well as overall survival for participants of the study with a 55 months median followup.

Last year when we had to decide on chemotherapy, TAC looked promising but with only 33 months median followup there was still some risk that the benefit would not be sustained--and could even reverse--in the long run. The only certainty about TAC was that it would have the toughest side-effects of all the alternatives her doctors offered. Now with this additional followup data Ann feels that the extra suffering she endured as a result of taking Taxotere may have some benefit. (She still has problems walking because of the nerve damage in her toes, a side-effect of Taxotere from which she is expected to recover fully.) We are very pleased and relieved to find that TAC's benefits appear to be sustained over the long term.

Our second bit of good news is that Ann's breast cancer did not result from genetic mutations that she inherited. Mutations in either of two genes known as BRCA1 and BRCA2 are responsible inherited breast cancer. The vast majority of breast cancer cases are not the result of BRCA1 or BRCA2 mutations. Nevertheless, Dr. Wendy Rubinstein, Director of the Center for Medical Genetics at Evanston Northwestern Healthcare, recommended reviewing Ann's family tree for others with cancer because Ann was so young when diagnosed. It would be important to know if Ann had BRCA1 or BRCA2 mutations because it would impact her breast cancer treatment as well as expose her to a high risk of ovarian, pancreatic, and possibly other cancers. (Links to online information about BRCA1 and BRCA2 are below.) Several weeks (and many phone calls to aunts and cousins) later Dr. Rubinstein received Ann's detailed pedigree. Based on this chart, Dr. Rubinstein concluded that there was less than a 1% chance that Ann had inherited mutations in BRCA1 or BRCA2. We are very pleased to confirm that neither Ann nor her siblings, nieces, and nephews have to worry about these mutations and their cause for breast and other cancers.

As I said at the beginning of this update, it's been a year since Ann's diagnosis. We are getting on with our lives and putting cancer in its place. The fog of chemotherapy side-effects continues to lift and we enjoy the clearer days. Unfortunately, there is no going back to "normal" and forgetting that this ever happened; Ann's omnipresent lymphedema is a daily reminder and it places real limits on our lives. But, these are limits that we are gradually coming to understand, accept, and work within.

Right now, we are busy getting ready for TWO Christmases, one this weekend with Ann's family and the other with Nello's on the traditional date.

We've said it many times but we want you to know that you all have been wonderful support for both of us this past year. Thank you very much for your help and understanding.

We hope that your holiday plans are merry and bright.

Love,

Ann and Nello



HEALTH

Aventis Drug Aids Survival Rate
In Early Stage of Breast Cancer

By RON WINSLOW and JULIA FLYNN
Staff Reporters of THE WALL STREET JOURNAL


A chemotherapy cocktail including Aventis SA's Taxotere significantly improved survival for women with early stage breast cancer and decreased the likelihood their cancer would recur when compared with standard treatment, researchers reported.

In a study involving 1,491 women, 87% of those randomly assigned to a regimen involving Taxotere were still alive 55 months later, compared with 81% of those taking the commonly used treatment including a drug called 5-fluorouracil, or 5-FU. The study also found that 75% of women remained free of disease compared with 68% on the standard treatment. The results translated into a 30% reduction in risk of death and a 28% reduction in chances of a relapse of the cancer, researchers said.

"This is one of the largest effects we've ever seen in a breast-cancer chemotherapy trial,'' said John Mackey, a leader of the study and head of the Northern Alberta Breast Cancer Program at Cross Cancer Institute, Edmonton, Alberta. He presented the findings Friday night at the San Antonio Breast Cancer Symposium in Texas.

What impressed other cancer doctors is that the study-essentially a five-year follow-up-builds on the three-year results presented about two years ago. The "gold standard" in breast cancer is to see how well patients do five years after diagnosis, said Peter Ravdin, medical oncologist at University of Texas Health Science Center, San Antonio, who wasn't involved in the study. Often, early positive results don't hold up over a longer period.

"These results more than held up, they strengthened,'' Dr. Ravdin said. A nearly one-third reduction in risk of dying within five years "is quite a big step forward'' for breast cancer patients, he added.

About 60,000 American women and a total of 300,000 women world-wide are diagnosed each year with early stage breast cancer -- when tumors are confined to the breast and lymph nodes in the armpit. They typically have the tumors removed surgically and may undergo radiation treatment as well as chemotherapy over several months following surgery.

Dr. Mackey said the results suggest that if all newly diagnosed patients got the new regimen, it would mean 18,000 additional women would be alive five years after their diagnosis.

The current standard chemotherapy cocktail, FAC, includes 5-FU and two other drugs, Adriamycin and Cytoxan. In the study, patients got either the 5-FU or Taxotere, but the companion medicines remained the same. Dr. Mackey said the results were essentially the same for all women in the study -- whether they were pre- or postmenopausal and whether their tumors were considered sensitive to estrogen or not.

Taxotere is already approved for women with advanced, or metastatic, breast cancer, among other indications. Aventis, which supported the study, said it plans to use the results to file in the U.S., Europe and Japan in the first quarter of next year for approval to use the drug in early stage breast cancer.

The presentation of the findings at the meeting came on the heels of another report that was a boost for a new class of drugs called aromotase inhibitors in long-term treatment for some breast-cancer patients. Currently, women with what is characterized as estrogen-positive breast cancer take tamoxifen for as long as five years to help keep the tumors from coming back. The study, involving 448 post-menopausal women, found that switching from tamoxifen to AstraZeneca PLC's drug Arimidex significantly reduced chances of the cancer's recurrence.

A larger study, published recently in the New England Journal of Medicine, found that Femara, an aromatase inhibitor marketed by Novartis AG, sharply reduced risk of cancer recurrence among women starting the drug after completing five years on tamoxifen.

Separately, biotech company American Pharmaceutical Partners Inc. released the clinical data behind a previously reported study showing that its altered form of the breast cancer drug Taxol worked better at higher doses than the original drug, with a lesser incidence of most side effects. The company's formulation encapsulates the active ingredient of Bristol-Myers Squibb Co.'s Taxol, paclitaxel, in a protein called albumin.

In September, American Pharmaceutical said its drug, Abraxane, had outperformed Taxol in the late-stage study involving 454 patients with cancer that had spread to other parts of the body. It released the data Friday at the San Antonio cancer symposium. Because the altered drug is designed to lead to a safer treatment regimen, higher doses can be used. In the Phase III trial, American Pharmaceutical used 50% more paclitaxel than standard Taxol.

The company said 33% of patients receiving Abraxane for three weeks saw shrinkages in their tumors compared with 19% of those taking Taxol over the same period, a difference that was highly statistically significant, according to Reuters news service. Moreover, the average patient taking Abraxane did not experience a worsening of symptoms for 21.9 weeks, compared with 16.1 weeks for those on Taxol, also a statistically significant advantage.

Write to Ron Winslow at ron.winslow@wsj.com and Julia Flynn at julia.flynn@wsj.com

Updated December 8, 2003 1:06 a.m.




TAC Links

Description of the Breast Cancer International Research Group (BCIRG) study and their protocol:

http://www.bcirg.org/Internet/Studies/BCIRG+001.htm


Abstract and slides from SABCS presentation:

http://www.abstracts2view.com/bcs03/view.php?nu=BCS3L_775
http://www.aventis.com/main/attachments/98944820031208104011.pdf


On-demand audio re-broadcast of a 8-Dec-2003 conference call (by Aventis, the manufacturer of Taxotere) includes the SABCS presenter walking though his slides:

http://aventis.nc3.de/webcast_2003_sabcs/popup.htm


Additional information about the study (mostly press releases) is available on the web:

http://www.medicine-news.com/articles/texte/2003/December/text1.html
http://www.aventis.com/main/page.asp?pageid=61596220031205002009&lang=en
http://www.eurekalert.org/pub_releases/2003-12/cw-mai120503.php





April 22, 2003

Aging Well

To know your health risks, know your family history

By KELLY GREENE
Staff Reporter of THE WALL STREET JOURNAL


When her extended family got together for dinner before a cousin's wedding last year, Kiplyn Primus, a 41-year-old marketing consultant in Atlanta, put together a notebook with information about the few diseases she knew her relatives had suffered from and passed out copies.

"Then we started talking," she says.

Ms. Primus soon learned that the "stomach complications" she had been told her grandmother died from were actually a form of stomach cancer. Another important discovery: Her cousin suffers from a heart murmur, just like Ms. Primus and her sister. "Now we know to watch for that in my sister's and cousin's children," she says.

It was tough to extract some details from her mother and aunt about the ages at which things happened to them and other older relatives, she confesses. Getting them to pinpoint "when they went through menopause was like pulling teeth from chickens," Ms. Primus says. "But I think even then they saw the importance of it. There is another generation that needs to be aware of what's going on."

Uncovering Pedigrees

More and more people are seeking out their family's health history, also called a "pedigree" by geneticists. As baby boomers age, they are gathering such data to gird themselves against the onslaught of such ailments as heart disease, breast cancer and diabetes that typically strike in later life. Scientific findings that link groups of genes to the predisposition for many chronic illnesses are spurring baby boomers' efforts to uncover their pedigrees.

In the past, "when someone said Uncle Joe died of cancer, that was all you heard," says Carol Daus, author of "Past Imperfect: How Tracing Your Family Medical History Can Save Your Life." "Now, if someone in your family has breast cancer, you can find out if you have the gene that's related."

She decided to delve into her own family's health history after her mother was diagnosed with breast cancer in her mid-60s. Ms. Daus, who is 44 and the mother of three children in Huntington Beach, Calif., discovered that breast cancer should be the least of her worries. It turned out that her family's real demon is cardiovascular disease, "but I didn't realize it until it was on paper staring me in the face." Her father developed heart disease in his late 40s and died at age 59 of a ruptured aneurysm; her two brothers have high blood pressure; and her grandmother had a debilitating stroke when she was 49 years old.

Actually, lots of people, whether they realize it or not, have taken a cursory stab at writing down health problems in their family tree. Think about it: When you visit a doctor, you're usually asked to fill out forms with questions about illnesses that you and other family members might have had. Unfortunately, that's as far as most people get.

"We keep better track of when we change the oil in our cars," says Ms. Daus. "But this information is so vital, and it's so scattered in most people's minds."

The Third Degree

So, what's the best way to reconstruct your family's health history? Shoot for at least three generations. Your parents, siblings and children are known as "first-degree relatives" in genetics lingo; grandparents and grandchildren are "second-degree." Go horizontally as well as vertically, including aunts, uncles and cousins. The more relatives you include, the better. Information about any ailment may prove helpful, so don't leave out illnesses because you don't think there's a genetic link. Be sure to note conditions that are potentially preventable, including high blood pressure, heart disease, diabetes, depression and alcoholism. And include the age at which the relative was diagnosed.

Finally, include other habits that could have an impact on overall health, including smoking, drinking, eating and lack of exercise, says Robin Bennett, a Seattle geneticist who wrote "The Practical Guide to the Genetic Family History."

For family members who have died, try to pinpoint when they died, the cause of death and -- at least as important -- any disease or condition that led to that cause of death. Maybe pneumonia was the cause of death, but that pneumonia was really triggered by a long-term chronic illness, for example.

Ms. Daus managed to get almost all the information she needed by talking to relatives. But if you find yourself running into roadblocks, every state has a bureau of vital statistics to which you can write to get death certificates. (Unofficial copies are often cheaper and easier to get than certified copies.) As with other genealogy projects, one of the best resources is the Family History Library, run by the Church of Jesus Christ of Latter-Day Saints in Salt Lake City (<http://www.familysearch.org>).

One caveat: Death certificates, particularly older ones, can be vague and misleading, says Aubrey Milunsky, a genetics professor at Boston University School of Medicine and author of "Your Genetic Destiny." And keep in mind that medical terminology has changed through the years. For instance, "dropsy" usually means "congestive heart failure," and a "tumor" can refer to many forms of cancer. Dr. Milunsky suggests digging into medical records when at all possible.

Look for Patterns

But even if you're left with questions, don't despair. "You're getting things down on paper and seeing if patterns develop," says Ms. Daus. Things to spot: Anyone who died of illness at a young age (generally before age 55), the same cancer among relatives, more than one cancer in one relative, and the same illness in more than one generation.

"When you start seeing recurring messages -- three or four relatives with diabetes, not all of whom are actually overweight, or you find two female relatives with breast cancer, that's when family history starts showing you have risk factors," says Joann Boughman, executive vice president of the American Society of Human Genetics, a professional group for geneticists in Bethesda, Md.

Here are some diseases for which family history increases your risk:

*Heart disease:
Risk increases with a history among your mother, father, or other relatives on either side, including bypass surgery on your father before age 55 or your mother before age 65.

*Stroke:
Twice the risk if a first-degree relative is affected.

*Colorectal cancer:
There's double the risk if you have at least one relative with the disease.

*Type 2 diabetes:
The risk increases with earlier age of onset in relatives and the number affected.

*Cancer:
Look for links among types that involve the same gene mutations, such as breast, ovarian and prostate. And don't overlook the breast-cancer history on the paternal side of your family.


It's also important to recognize when the risk of getting a disease is not necessarily heightened by family ties. The genetic risk for Alzheimer's disease, for example, decreases dramatically between the ages of 60 and 85. "It doesn't look like genetic factors play a role at all by the mid-80s," says Jeremy Silverman, an associate professor of psychiatry at Mount Sinai School of Medicine in New York. In other words, if you have a family member who contracted Alzheimer's after age 85, as many people do, there's little cause for worry.

Once you've compiled your family tree, you might want to get some professional help interpreting it. William Hall, an internist and geriatrician at the University of Rochester School of Medicine in New York, says that he sees increasing numbers of patients coming to him with family health histories, which helps them to develop "a much more collaborative relationship" with their doctor.

"Maybe the greatest benefit is that it allows us to reflect more carefully about the many things we can do proactively for ourselves regardless of our hereditary makeup," says Dr. Hall.

Ms. Daus, for example, realizing how many of her relatives suffered from heart disease, started exercising much more regularly, and now spends at least 30 minutes every day either at the gym or on her treadmill at home. She even read "Fast Food Nation: The Dark Side of the All-American Meal" aloud to her children, "and they won't even set foot in a McDonald's" now, she says proudly.

Write to Kelly Greene at kelly.greene@wsj.com


Shaking the Tree

Two resources to help you start a family health history

*CDC Family History Survey
http://www.cdc.gov/genomics/info/conference/FHSurvey.htm

Scientists are still tinkering with this tool, but it already offers a common list of diseases and conditions that afflict many families


*American Medical Association
http://www.ama-assn.org/ama/pub/printcat/2380.html

Aimed at physicians, this Web site includes a family-history form much like the one you could expect to get at a doctor's office






BRCA1 and BRCA2 Links

Understanding the relation between genetics and breast cancer

http://www.curetoday.com/backissues/v2n3/departments/earlydetection/index.html


Prevalence of BRCA1 and BRCA2 mutations

http://www.myriadtests.com/provider/mutprev.htm


Benefits of testing for BRCA1 BRCA2

http://www.myriadtests.com/provider/benefits_brac.htm


How to gather family history information in preparation for genetic counseling

https://cancerhistory.myriadtests.com/myriadmain.php

Posted: Wed - December 17, 2003 at 04:58 PM        

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