Wednesday, July 30, 2008

Why I Relay

This mp3 file is a message recorded by myself to be aired on The Coast FM Classic Hits 95.5, Kincardine's very own radio station. The Kincardine Relay for Life's Entertainment Chair, Mike Brough, asked all the team captains to record a message about why they participate in Relay for Life. So, press play and listen to Why I Relay...

I relay in memory of my mother who lost a brief but brave battle with ovarian cancer in 2007.
I relay in honour of my father who is an 18 year survivor.
I relay for myself as a carrier of the breast and ovarian cancer gene mutation.
I relay in memory of those who have lost their fight.
I relay in honour of all those still fighting.
I relay for everyone whose lives have been touched by cancer.

Relay For Life is more than just raising money for a good cause, it is a way to honour and remember family and friends. It is a way for a community to comfort one another in their times of grief and celebrate in their times of joy. And it is a way to take up the fight against cancer, to change our future, so that one in three people will not be diagnosed with cancer, so that one day, we will have no reason to relay.

Friday, July 25, 2008

I Feel a Great Weight Has Been Lifted

I don't know where to start this post. If it seems all over the map, that's because I'm so happy, I don't know where to begin, so I'm just spewing everything out...hope it all makes sense!

I had my appointment this morning with Dr. Murial Brackstone. I spent just over an hour with a nurse practitioner, Margo L. Bettger-Hahn, RN, BScN, MScN, before I saw Dr. Brackstone. Margo is a Clinical Nurse Specialist, Breast Care and Plastic Surgery Programs. Margo is awesome! First she gave me a very thorough breast exam, then we talked and talked and talked. She answered all of my questions without me having to even ask. Right from the start, I told her I wasn't interested in surveillance, that I wanted a mastectomy. She just smiled and said good decision, that's what Dr. Brackstone would recommend anyway.

Margo L. Bettger-Hahn, RN, BScN, MScN
Clinical Nurse Specialist, Breast Care and Plastic Surgery Programs

When we were discussing reconstruction techniques, she asked me what type I was interested in. I told her I had been wanting FREE TRAM Flap because I didn't want the loss of abdominal muscle associated with a TRAM Flap. When I said this she asked me if I'd ever heard of a DIEP (Deep Inferior Epigastric Perforation) Flap...I nearly fell off my chair. That's the reconstruction I really wanted, but thought it wasn't being done much in Canada yet. She said that the plastic surgery team of Dr. Claire Temple and Dr. Douglas Ross (no, NOT George Clooney, although he's pretty damn good looking!) have been doing DIEP for just over a year now. You have no idea how happy this made me! I was hoping to get Dr. Temple; and getting Dr. Temple to do a DIEP is just so amazing to me! :)

The DIEP flap uses skin and fat from the lower abdomen. No muscle is taken with this procedure. An incision (surgical cut) is made in the lower abdomen and you receive a “tummy tuck” in addition to the breast reconstruction.

These pictures aren't accurate, as I will be having circumareolar (skin sparing) mastectomy.

After talking with Margo for over an hour, I then met Dr. Brackstone. She's fabulous too! She also gave me a breast exam. Then we discussed my BRCA2 status, surgery and my previous MRI results from April. The small "indeterminant" spot on my MRI was nothing; she said not to worry about it as it is a normal occurrance in an aging woman's breast (AAGH! aging!!!). We then discussed my BRCA2 status. She told me with my BRCA2 status (a major deletion mutation), my likelihood of developing breast cancer at some point is more like 99% (not the previous 80 - 90% I'd been told), so it may as well be 100%. She said mastectomy is really the only decision to make or else the stress and constant worry, will drive me nuts. I agree, it already is! I don't like the idea of having MRIs every 6 months for the rest of my life and constantly waiting for results. After my surgery and reconstruction, I will have a less than 2% chance of developing breast cancer (that's less than the general population) and will no longer need to have mammograms, ultrasounds or MRIs. There's no point because I will have no breast tissue left. She told me I will need to have the hysterectomy done first, because of the abdominal surgery involved with the DIEP. The only downside to the DEIP is that it will likely be a 10 to 12 hour surgery. DH isn't too thrilled with this idea (nor am I), but it is a complicated surgery because it's microsurgery and it'll be worth it in the end.

Dr. Muriel Brackstone, MD, FRCPC

Margo was going to send in my referral to the plastic surgeons today. Margo is also the nurse practitioner working with them with breast cancer and reconstruction patients. She told me when I have my referral with Drs. Temple and Ross, she will more than likely be there. She said if she's not, to have them page her and she'll be right there. How wonderful! I have a feeling Margo is going to be a big part of this for me and will be a great support.

Dr. Claire Temple, MD FRCSC

Dr. Douglas Ross, MD MEd FRCSC

Now it's not 100% a given that I can have this type of reconstruction, but she figured I was a good candidate for it. Once I receive my referrals to the plastic surgeons, they will discuss it with me, and will schedule me for a CT Scan to map out the arteries in my abdomen.

When I have the surgery, Dr. Brackstone will first remove the breast tissue. This is done by circumareolar (skin sparing) circular incision around the areola and nipple, leaving all the breast skin intact. She then removes all the breast tissue. She said her part's the easy part! Pathology will be done on all my breast tissue to make sure there is no cancer cells. Once she's done her part, then Drs. Temple and Ross will work their magic. I have included a description below of what DIEP is. After the DIEP surgery, there will 2 smaller surgeries later on. One to reconstruct nipples and one to tattoo the areola area. I did ask Margo about nipple sparing and she emphatically said "no way" since you would be leaving breast tissue behind. She said "don't worry, we'll make you some nice new ones!" :)

I feel so much better after today's appointment. Things are starting to move forward and I feel a huge weight has been lifted.

What is a DIEP flap?
DIEP stands for Deep Inferior Epigastric Perforator. This is the named vessel for which the tissue to be transferred is based. “Flap” is a plastic surgery term referring to the tissue which is to be transferred. The deep inferior epigastric vessels arise from the external iliac vessels (the external iliac vessels become the femoral vessels in the leg). The deep inferior epigastric vessels course beneath the rectus abdominus (the major abdominal “six pack” muscle) on each side. These vessels send off branches to the muscle as well as through the muscle into the overlying fat. These perforating branches are those which are identified, preserved and transferred with the overlying tummy fat to reconstruct the breast.

Definition DIEP Flap:

Perforator flaps represent the state of the art in breast reconstruction. Replacing the skin and soft tissue removed at mastectomy with soft, warm, living tissue is accomplished by borrowing skin and fatty tissue from the abdomen.

A slim incision along the bikini line is made much like that used for a tummy tuck. The necessary skin, soft tissue, and tiny feeding blood vessels are removed. These tiny blood vessels are matched to supplying vessels at the mastectomy site and reattached under a microscope.

Unlike conventional TRAM flap reconstructions, use of refined perforator flap techniques allow for collection of this tissue without sacrifice of underlying abdominal muscles. This tissue is then surgically transformed into a new breast mound. The abdomen is the most common donor site, since excess fat and skin are usually found in this area. In addition to reconstructing the breast the contour of the abdomen is often improved much like a tummy tuck.

Restoration of the nipple and areola follow. Scars fade substantially with time. For many women the reconstructed breast may be firmer and have a more youthful appearance than their natural breasts."

Tuesday, July 22, 2008

Today's appointment with Dr. Steve Power went extremely well. I just love Dr. Power, his beside manner is the best!!!

First, I got my CA-125 (carcinogenic antigen 125) blood test results. The results came back low, low, low, which is exactly what we want!!!

Dr. Power did another TVU (transvaginal ultrasound) and everything looks great! My uterus is normal, my right ovary is small and inactive and my left one was ovulating! YIPPEE!!!
Despite having some hot flashes and night sweats, this means I'm not quite at menopause...yet! It's wonderful having Dr. Power do the ultrasound...he explains everything you're seeing on the screen and there's no waiting for results.

We talked a little more about Dr. Vilos and the surgery. He again reiterated that Dr. Vilos is the best and I couldn't ask for a better gynaecological / laparoscopic surgeon. He said because of my BRCA2 status, an abdominal wash and pathology will be done on absolutely everything they remove just to make sure there are no cancer cells present at all.

Dr. Power doesn't want to see me again until after my surgery...unless it doesn't happen within the next 4 months; then he wants to see me again for another ultrasound. He figures I should have the surgery within a month or two of seeing Dr. Vilos. I'm not an emergency case, but am considered higher risk because of my BRCA2 status and will more than likely get bumped up the surgical list.

That's about it! It's off to see the breast oncologist, Dr. Muriel Brackstone, on Friday.

Sunday, July 20, 2008

Feeling Anxious!

I'm starting to get pretty anxious again. Time sure flies! It seemed like forever before I had my doctors' appointments and look at that calendar! I have 2 this week.

I see my gynaecologist, Dr. Steve Power, again this Tuesday. Unfortunately DH is unable to attend with me this time, so I'll be heading to London alone. All should be fine though, this is just a follow-up. I have a pile of questions to ask him, so hopefully we'll get a chance to have a long talk. I've made myself a list this time so I don't forget to ask anything!!! Instead of having just the prophylactic salpingo-oophorectomy (removal of tubes and ovaries), I'm going to opt for a total hysterectomy. If I'm going to go this far to avoid cancer, I may as well try to avoid all female cancers. With no tubes and ovaries, I don't need a uterus. "Why keep the basket if you have no eggs!"

Unfortunately, I don't see the gynaecological laparoscopy specialist until the end of August. I'm hoping this can be done by laparoscopic assisted vaginal hysterectomy, however Dr. Power was unsure if I am a candidate for laparoscopy because of a HUGE abdominal incision I have from liver surgery in 1992. I just want this surgery done so badly that I don't care and will do the abdominal surgery just to get this over with. I'm very anxious as it is recommended this surgery be done by the age of 45 and I'm let's "gid 'er done"!

Then, this coming Friday, I finally get to see the breast oncologist, Dr. Muriel Brackstone. DH is able to attend this one...I'm glad. I have a lot of questions to ask her as well and have made myself a list for her too so I don't forget anything. I've pretty much made my decision and I'm not going to opt for the surveillance route; I'm going to ask for a bilateral mastectomy. I've done tons of research on various reconstruction options and surgeries, so will discuss those with her, however, I imagine for most Q&As I will have to wait until I get a referral to a plastic surgeon. I'm hoping I'm a candidate for nipple-sparing FREE (muscle sparing) TRAM Flap (transverse rectus abdominous myocutaneous flap: a type of reconstructive surgery). I love the idea of using my own body to reconstruct my breasts as opposed to silicone implants. And as an added bonus, one of the "side effects" of a TRAM Flap is a permanent tummy tuck!!! If I am not a candidate, then I will go for implants. I'm hoping the wait for that referral won't be so long.

There may be the possibility of doing both surgeries at once. This is a much longer and complicated surgery (ranging from 8 - 12 hours), with a longer hospital stay and recovery time, but it would be one or two less surgeries. I don't know if this is an option, but it won't hurt to ask!

If anyone has any suggestions of questions I should ask, feel free to send 'em along!

Wednesday, July 9, 2008

NIH, Sanger Researchers Develop Assay for Assessing BRCA2 Variants

NIH, Sanger Researchers Develop Assay for Assessing BRCA2 Variants
[July 8, 2008]

By Andrea Anderson, a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – Scientists have developed a functional assay for distinguishing between dangerous and neutral mutations in a breast cancer susceptibility gene.

In a paper appearing online in
Nature Medicine this past Sunday, researchers from the National Cancer Institute and the Wellcome Trust Sanger Institute described how they used mouse embryonic stem cells to evaluate the functional implications of 17 BRCA2 sequence variants. They found that this assay could effectively and reliably categorize risky BRCA2 mutations — which can dramatically increase an individual’s risk of breast and ovarian cancer — as well as relatively innocuous mutations.

“Our assay is likely to improve our understanding of unclassified mutations because it allows for analysis of all types of BRCA2 mutations,” senior author Shyam Sharan, head of NCI’s Genetics of Cancer Susceptibility Section, said in a statement.

BRCA1 and BRCA2 mutations, which tend to be inherited in some families, can dramatically increase an individual’s cancer risk. For instance, those carrying a mutation in one of the genes have a 35 percent to 80 percent risk of developing breast cancer by their 70th birthday. In contrast, the average American woman has a 12.3 percent risk of developing breast cancer in that time.

But BRCA1 and BRCA2 sequence variants don’t all confer the same risk. Some are extremely deleterious (unfortunatly, that's what mine is...the complete Exon 19 is missing)
while others are neutral or low risk. Distinguishing between these extremes can be tricky, since mutations are often identified through genetic tests of families with a history of breast and ovarian cancer.

“Segregation analysis in cancer-afflicted families provides the most reliable information to distinguish between deleterious and neutral alterations identified in BRCA1 or BRCA2,” Sharan and his colleagues wrote. “However, there is an enormous need for a functional assay to classify variants for which such information is not available, because most mutations are rare, and familial data are often insufficient.”

That also makes it difficult to interpret BRCA1/BRCA2 genetic tests for those carrying unclassified or minor mutations — such as the 1,900 known BRCA1 or BRCA2 variations that don’t disrupt the gene product in an obvious way but may still affect gene function.

For this study, Sharan and his team exploited the properties of mouse embryonic stem cells to develop an assay for systematically testing BRCA2 variants. Specifically, the researchers took advantage of the fact that mouse stem cells need a functional copy of BRCA2 to survive.

The human BRCA2 gene can complement — that is, take over the function of — mouse BRCA2, but only if the human BRCA2 gene is functional. To test the functionality of various BRCA2 sequence variants, the team generated mouse embryonic stem cells that were missing one copy of BRCA2 and one conditional BRCA2 allele.

Then, they added bacterial artificial chromosomes containing individual human BRCA2 variants, inactivated the lone copy of mouse BRCA2, and looked at whether the cells could survive by relying on that human BRCA2 gene.

Variants that could not rescue the BRCA2 function in these mouse embryonic stem cells were classified as deleterious mutations, while those that could were considered neutral mutations. The researchers further characterized the variants using plating efficiency experiments and testing the cells’ sensitivity to DNA-damaging agents.

All told, the researchers tested 17 BRCA2 variants. As expected, mutations with known functional effects could not rescue the BRCA2 function while neutral mutations could. Among the previously unclassified variants, they found examples of both neutral and deleterious variants. Overall, the researchers classified eight of the 17 mutations as deleterious. The remaining nine appear to be either neutral or low risk.

While the researchers emphasized the assay’s promise for evaluating BRCA2 variants, they were quick to note that it will take time before the assay can be used as a clinical tool. “[U]ntil the assay is fully validated,” the authors warned, “caution must be exercised when using these data to make clinical decisions.”

According to a statement from the National Institutes of Health press office, Sharan is interested in collaborating with commercial organizations to develop the diagnostic test.

In the meantime, the authors are optimistic that such assays will eventually be used to characterize not only BRCA2 variants, but also variants in other disease-associated genes.

“We have established that this assay is accurate and is one of the most comprehensive among those available to date, allowing analysis of virtually any type of mutation,” they wrote, “and it may also serve as a model for investigating other human disease-associated genes that result in a phenotype detectable
in [embryonic stem] cells.”

2008 Breast Cancer Wait Times in Canada Report Card

Report from the Canadian Breast Cancer Network.

2008 Breast Cancer Wait Times in Canada Report Card (pdf document opens in new window)

Tuesday, July 8, 2008

BRCA2 and Resistance To Therapy

This was previously released in February. I found it while doing some research. This may explain why my mom didn’t respond well to chemotherapy treatments. Cisplatin was one of the chemo drugs mom was given. Looks like BRCA2 mutations, can mutate again to resist certain chemo. This is very very scary...

Taken from HUM-MOLGEN News

Scientists have gained new insight into how changes in BRCA2 can affect a cancer's resistance to therapy. BRCA2 mutations are associated with an increase in breast and ovarian cancer risk, as the gene's normal function is to repair damaged DNA. But these cancer-causing faults are bad news for the tumour itself, as they also render it sensitive to DNA-damaging chemotherapy drugs like cisplatin. Unfortunately, many BRCA2 tumours develop resistance to cisplatin.

Two papers published online in
Nature reveal how this resistance occurs. The teams, led by Alan Ashworth and Toshiyasu Taniguchi, show that some cancer cells can acquire secondary 'reactivating' mutations in their BRCA2 gene, switching it back on and allowing the cancer to repair the DNA damaged by the drug's assault. Such mutations were found in several cisplatin-resistant ovarian cancer patients. The discovery raises the possibility that blocking BRCA2 function in such patients might allow doctors to overcome drug resistance and continue with cisplatin treatment.

Alan Ashworth (The Institute of Cancer Research, London, UK)
Toshiyasu Taniguchi (Fred Hutchinson Cancer Research Center, Seattle, WA, USA)

Abstract from Author, Toshiyasu Taniguchi's Paper:

Ovarian carcinomas with mutations in the tumour suppressor BRCA2 are particularly sensitive to platinum compounds. However, such carcinomas ultimately develop cisplatin resistance. The mechanism of that resistance is largely unknown. Here we show that acquired resistance to cisplatin can be mediated by secondary intragenic mutations in BRCA2 that restore the wild-type BRCA2 reading frame. First, in a cisplatin-resistant BRCA2-mutated breast-cancer cell line, HCC1428, a secondary genetic change in BRCA2 rescued BRCA2 function. Second, cisplatin selection of a BRCA2-mutated pancreatic cancer cell line, Capan-1, led to five different secondary mutations that restored the wild-type BRCA2 reading frame. All clones with secondary mutations were resistant both to cisplatin and to a poly(ADP-ribose) polymerase (PARP) inhibitor (AG14361). Finally, we evaluated recurrent cancers from patients whose primary BRCA2-mutated ovarian carcinomas were treated with cisplatin. The recurrent tumour that acquired cisplatin resistance had undergone reversion of its BRCA2 mutation. Our results suggest that secondary mutations that restore the wild-type BRCA2 reading frame may be a major clinical mediator of acquired resistance to platinum-based chemotherapy.