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Genes at Guys

Interesting day at Guys Genetic Centre today. When I had my BRACA test it was negative, but they identified a BRIP1 mutated gene, which is a lower than BRACA cause of OC, but still significant. My daughter decided to be tested, so we went to see a geneticist , who talked her through the process. If she is positive they are very clear that she should have her ovaries and Fallopian tubes removed.

So she went to have the blood lest. She didn't actually faint, but it was close! Can't imagine how she would get through surgery. She is genuinely needle phobic. Oddly enough I discovered recently that both her brothers are too. Now there's a useful genetic link!

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Hi Rachael, thanks for posting. Glad you have a negative BRCA test. As for the other gene thats been found if your daughter has it she can do something proactive about her chance of getting oc.

I am very interested in this & wanted to know if you paid privately for that or was it part of the NHs?

I have had a negative BRCA test so has the other members in my family but we still no nearer to finding the gene that has killed 3 of my family & left 2 others having breast cancer & me fighting oc.

Please keep us up datted on your daughter's results because it can help others on here & I am keeping my finger cross she is ok. Good luck thinking of you take care Cindyxx

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They are doing more and more work on genes these days - they have only been looking at BRIP1 for the past year apparently. Maybe as time goes on they will find a common gene in your family. Which is not much comfort to you at the moment!

I had the BRAC test on the NHS (thank you Nye) and they they tested for other genetic malfunctions at the same time. Kate's test was also on the NHS. She asked if surgery would also be NHS as it would be elective, and was told that if her result was positive it would be classed as necessary.

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Hi Rachael, thanks for that. I have asked my onc many times about gene testing they did do the BRAC1/2 it was negative but won't offer me any more kind of gene testing on the NHS. I was going to ask them if they could recommend a private gene testing company. Like you I have family & want to know if I have pasted it on. It's information like this that really helps ladies like me. Take care love Cindyxx

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Hi Rachael I also have the rare BRIP1 mutated Gene. I have 3 daughters, 40, 37 & 27 who have all been tested and are clear. At least it stops with me. They all have been told that once they reach 45-50 they should seriously think about having their ovaries and fallopian tubes removed. I am just thankful that they are now on the radar and that me having BRIP1 will give the genetic people the ability to find out more. Take care xx Angie

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Angie,

I can understand the doctor advising your daughters to wait on having the Ovaries removed until they are 45 (or post-menopausal), but question why they should wait on the Fallopian Tubes.

If they are through having children, instead of the Tubal Ligation or the more recent Tubal scarring, the tubes could be removed Laproscopically in a 30 minute outpatient procedure.

Recent research has definitely proven Fallopian tissue was the source for at least 75% of the 60 types of Ovarian cancer. Leaving the tubes in place after child bearing is complete, leaves the greatest source for Ovarian cancer in place.

Both Angelina Jolie and Christina Applegate had their tubes and Ovaries removed due to their higher risk for Ovarian cancer.

If the Salpingoectomy (the procedure for removing the Fallopian Tubes) were to become more common, we could expect to see a reduction in both the number of cases of Ovarian cancer as well as the number of lives lost to it.

Ovarian cancer is the fifth leading cause of cancer deaths among women in the US annually, having surpassed Cervical cancer since the introduction of the Pap Smear.

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Thank you for your reply. I will pose the question to my girls. My eldest has one child and doesnt want anymore, the middle one is adamant that she doesn't want any but that may change as she nears 40 and the youngest would love to have children but hasn't found the right partner. I am sure they will do the right thing as they have seen what i am going through. Take care

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The geneticist who talked to Kate said that the BRIP1 OC tended to occur in women over 60, and that she would want Kate to have been through the menopause before any operation.

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It’s also a decision they should discuss with their doctor.

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Hi DBeavears, my OC started in my right Fallopian tube. As you say, most OC does. I don't think this is widely known, especially about the possibility of preventative salpingectomy, with FH. Why do you think we don't hear much about it? Is it more widely known in the US? Linda x

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I don’t have a clue why doctors are so reluctant to remove the Fallopian Tubes at least in the BRCA Positive women. It can be done Laproscopically as an outpatient. A 15 minute procedure per side, with a single stitch per tiny incision, and back to work the next day.

It may be that the insurance companies will pay for the Tubal Ligation or scarring procedures which are effective in 99% of pregnancies (definite cost savings for insurance companies), but not the removal.

There is a 6 1/2 years time delay from Fallopian cancer cells appearing to Ovarian cancer.

If a study could be done, removing the Fallopian Tubes instead of the standard Tubal Ligation, then track those women for seven years, there should be a significant drop in the number of cases of OvCa - possibly enough to demonstrate cost effectiveness, as the 15 minute Salpingoectomy couldn’t cost that much more than the alternatives for preventing pregnancies.

If my wife could have had the procedure instead of the Tubal Ligation, it’s very likely she would still be with me. That is the reason I put her photo in my ID.

Her OvCa was identified on a Monday, and she was gone less than four days later - just 60 hours after her first Chemo treatment. She’s the reason why I post in this and other forums.

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You have done a lot of reading & research DBeavers - I am sure this will all raise awareness in the future. So sorry to hear of your loss, that was very rapid. BW

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There’s so much information out there it takes a while to absorb it all. It helps me understand the need for Gynecological-oncologists, as there just too much for the basic gynecologist to try to stay current with all the advances just in the area of woman-only cancerstypes of Ovarian Cancer.

Consider that of the 60 different types of OvCa, 45 of them start from Fallopian tissue and migrate to the Ovaries. This in addition to the separate Fallopian, Uterine, peritoneal, Vulvar, Vaginal, and Cervical cancers.

The various types of Epithelial Ovarian cancers can appear in the fertile or Post-menopausal years, presenting different symptoms. My wife had one of the Epithilial types that may or may not produce cysts, tumors, or other abnormal growths. Nothing showed up on her X-rays, Trans-vaginal Ultrasound, or CT Scans. It took a PET scan to identify the hot spots on both lungs, both ovaries, her liver and oomentum (abdominal wall) to confirm it was Ovarian.

And the first treatment may be wrong if the oncologist doesn’t know the patient’s BRCA status. The time to get the genetic testing is before a cancer appears, if cancer runs in the family.

Recent research with the past five years have added Prostate and Pancreatic cancer to the previously known Breast, Ovarian, and Colo-rectal cancers that are linked to the BRCA mutations. A person who has two cases of those five specific cancers should consult a specialist to see if they should have genetic testing. There are a multitude of mutations possible on the BRCA 1 & 2 genes, so the testing can take two or more weeks, while the patient is possibly on the wrong treatment that is the standard protocol.

An inherited mutation on the BRCA genes WILL be passed on to 50% of the children, so one more reason to consider getting tested. The Family Practice Physcian and OB-Gyn can’t be alert to a patient’s risk if the woman hasn’t been tested.

And this doesn’t even scratch the surface.

I’m still learning.

.

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Hi. Have you thought of writing it all up?

I am going to be tested for BRCA 1&2. Had to ask for it. No FH but it does/can influence treatment options, as you say.

Best wishes, Linda

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Linda,

I haven’t printed it, but I share every chance I get. All my replies here on Ovacome, overcome, Twitter, and Facebook are off the cuff. I rarely have to look up any facts, statistics, websites p, etc.p, as it stays fresh and on the tip of my tongue/front of the brain. As I learn somethings new related to Ovarian cancer, I’ll file it with the appropriate data already stored in my gray matter.

Using a note card or two for outline, I can talk extemporaneously for two hours on this subject that is so close to my heart, and then take questions and answers.

On average, I set up my Teal Awareness table one two three times a month in groups or public events to share what I have learned while handing out cups, magnets, and symptom with the BEAT symptoms on them.

I could probably quote the top four symptoms backwards or forward in my sleep after sharing them with more than 5000 over the past two years face to face, plus with hundreds more online.

The hardest question to answer was after the Abcodia Corp. brought the British researched ROKA Test to the US and had approval of 46 state medical boards, why did the FDA rule against women paying for and having this optional test that had proven to be twice as accurate at confirming OvCa in Stage I or II than the CA-125 blood test without all the false positives and false negatives.

There is no good answer, other than talk to their doctor and search for the test online from a Canadian source.

I don’t have a website or blog, so other than printing up handout sheets, where would I use the write-up?

As for your being tested for the BRCA mutations, a Positive will also indicate the need for testing your children since it doesn’t skip a generation, being passed on to 50% of your children.

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Hi DBeavers, I think some nuance is important with regards to quoting statistics. With a genetic mutation such as BRCA, there is a 50% chance of passing on the mutation. This is not the same as saying that '50% of your children WILL carry the mutation.' Please bear in mind that the majority of people here have (as I know you have) been affected by Ovarian Cancer. Many will be coming to terms with all of its implications. One of the great strengths of this forum is that posters try hard to find the balance between providing accurate information in a way that is also supportive of the members.

I know how important it is to raise awareness. Many of us, like you, desperately want to use our experiences to make things easier for women and their families in the future. I have read with admiration how much you do to spread the word of symptoms and appreciate your motives for this. Best wishes Sx

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Linda,

I just received this info on the Fallopian Tube removal as an alternative surgery. Studies being done in both Canada and the US.

Doctors pushed for it, M.D. Anderson Hosp. In Texas is one of seven participating in the US study, where the women will be tracked for more than a decade to compare high risk (BRCA Positive) women who had just the Salpingectomy vs. the standard Ovaries and Fallopian Tubes removed at the same time, along with those who were counseled but opted out.

This could give the results to show the need for a larger sampling that could make the Salpingectomy a standar procedure for women who have completed their childbirth cycle, with the Ovaries to be removed at 40 or 45 depending on whether they have the BRCA 1 or 2 mutation.

Anna Hargrove learned she carries a genetic mutation that predisposes women toward breast and ovarian cancer at 27, which was no surprise given her family history.

Hargrove, cautious by nature, did what a lot of women with the mutation do: she underwent a double mastectomy. She then proceeded to get married, deliver three children and, soon after her 40th birthday three weeks ago, have surgery to reduce the risk of ovarian cancer.

But there was one significant difference: the procedure didn’t involve her ovaries.

Instead, MD Anderson Cancer Center surgeons removed Hargroves’ fallopian tubes, part of an experimental study investigating whether taking out only the slender ducts that carry eggs can prevent the devastating disease, at least in the short run. The idea, based on a relatively recent discovery that ovarian cancers often start in the fallopian tubes, is to delay menopause prematurely brought on by the removal of the ovaries, the recommended course of action for women at high risk.

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"Who wants to go through menopause at 40?" asks Hargrove, an Austin stay-at-home mom whose mother was diagnosed with breast cancer when she 37 and whose grandmother died of the disease when she was 67. "I was prepared to do it, but when MD Anderson gave me the option of just removing my tubes I jumped at it."

‘Guinea pig’ patients?

The idea is controversial in some cancer-care circles — critics say the women are guinea pigs assuming an unknown degree of risk — but if the study is successful, it could dramatically change the way doctors and their patients approach the prospect of ovarian cancer, one of the most lethal types of the disease.

The practice eventually might benefit not just women with one of the mutations but also perhaps many not at high risk. Another study, currently being conducted in Canada, is investigating the approach in women without such a mutation who don’t want to have any more children and were planning to have their tubes tied. Instead, they’re having the fallopian tubes removed and being tracked in the coming decades to determine whether their absence decreases women’s odds of developing ovarian cancer.

A better approach certainly would be welcome. Ovarian cancer mortality rates have declined only slightly in the nearly half century since President Richard Nixon declared the War on Cancer, and the five-year survival rate ranges from 10 percent to 40 percent when the cancer has spread, depending on how much. It kills about 14,000 U.S. women annually.

There is no screening test and because the disease produces no obvious symptoms, it typically remains undetected as it silently grows.

That’s why doctors recommend women who have a mutation in either the BRCA1 or BRCA2 genes — mutations that allow cells to develop instability that can lead to cancer — have their ovaries removed not long after childbirth is done, drastic as that may sound. Compared to the general population’s 1 percent risk of developing ovarian cancer, women with BRCA1 and BRCA2 mutations have a 39 percent and 17 percent risk, respectively. Women are advised to have their ovaries removed by 40 if they have a BRCA1 mutation, by 45 if they have the BRCA 2 mutation.

Removing the fallopian tubes and ovaries eliminates the possibility of ovarian cancer, though a less than 5 percent risk of a related cancer nearby remains, says the principal investigator of the study. And because the ovaries make estrogen, the hormone that fuels many breast cancers, their removal reduces that risk by 50 percent too, according to the National Cancer Institute.

The problem is that the removal of the ovaries brings on menopause 10 to 15 years before its normal onset. In their late 30s or early 40s, such women suddenly start experiencing hot flashes, vaginal dryness, painful intercourse and decreased libido. They also develop a higher risk for developing heart disease and osteoporosis.

"Menopause has such a huge impact on quality of life and even feelings of being a woman," says Dr. Karen Lu, the study’s principal investigator and MD Anderson’s chair of gynecologic oncology and reproductive medicine. "It’s a life-changing time."

A disease origin hint

Following surgeries on BRCA mutation carriers in the 1990s and 2000s, Lu was one of a number of pioneers who documented evidence of cancer in the fallopian tubes but not yet in the ovaries, the key impetus for the new research. Before that, statistics showing women who had their tubes tied developed ovarian cancer 50 percent less often than women who didn’t was a hint that the disease might originate in the tubes.

That discovery was not lost on the ovarian cancer advocacy community, desperate for a new strategy better balancing risks and quality of life. Lu emphasizes that they pushed for the study, which still calls for the removal of the ovaries. Removing the tubes at an earlier time just buys women at risk additional time before the plunge into menopause.

The push speaks to the change from 15 or more years ago, when Lu’s patients at risk for ovarian cancer were mostly women with breast cancer, typically already in menopause as a result of their treatment with chemotherapy. Due to the increase in genetic testing, Lu says, her at-risk patients now arrive at a younger age, cancer-free, pre-menopausal and faced with hard decisions about how to respond.

Some decide to roll the dice and keep their ovaries. The new approach would give them another option.

A gutsy decision

Dr. Christopher Crum, a pathologist at Boston’s Brigham and Women’s Hospital and another discoverer of ovarian cancer’s roots in the fallopian tubes, isn’t so sure it’s a good idea yet to remove only the tubes as an intermediary step. He worries because researchers haven’t been able to trace some advanced malignancies back to the fallopian tubes.

“If you’re wrong, you’re looking at some women whose decision at 40 may mean they’re never going to see their grandchildren,” says Crum. “It makes me pretty nervous. I think women opting to just have their tubes removed have a lot of guts.”

Lu, who knows ovarian cancer’s ravages all too well from caring for such patients, acknowledges the trial makes her nervous too. But she says such research is the responsible thing to do so doctors can counsel women not inclined to have their ovaries taken out whether removing their tubes is a reasonable option.

The rules call for the study to be stopped if more than two women develop ovarian cancer, something Lu doesn’t anticipate given existing data on when cancer originates in the fallopian tubes or ovaries in BRCA patients. Lu also says that the vast majority of ovarian cancer originates in the fallopian tubes in BRCA patients. Most of the ovarian cancers not traceable to the tubes occur in women without such a mutation, she says.

Lu says it will take a bigger study for the idea to be accepted, likely one with 1,000 or more patients. The current study, 18 months in and about halfway through, will enroll 270 patients at seven institutions around the nation — half will have their tubes and ovaries removed and half will have just their tubes removed initially, advised to follow up with the ovaries by the BRCA1 and BRCA2 recommended removal dates. Patients who wait until later to have them removed or eschew such removal altogether also will provide useful information, Lu noted.

Protection without sacrifice

Women with a genetic mutation that predisposes them to ovarian cancer represent only 20 percent of the roughly 22,000 diagnoses annually. Trials like the Canadian one being conducted on lower-risk women who had planned on having their tubes tied could show a wider application. But results won’t be known for decades, inasmuch as ovarian cancer’s average age of diagnosis is 60. Even then, assuming the trial shows a benefit, it likely would require discussion of whether such tube removal would be a smart policy recommendation in low-risk women not planning on getting them tied.

For now, BRCA patients participating in the research express happiness to have a new option. Hargrove, who has the BRCA2 mutation and plans to have her ovaries removed at 45, says she feels good about the future because “knock on wood, family members only had breast cancer, not ovarian cancer, and this approach is still pretty conservative.”

Some patients, like Amy Starr, have already finished the two-step process. A BRCA1 carrier who who took the test hoping it would prove that she didn’t have a mutation and put her mind at rest, she had her tubes removed at 37 as part of an MD Anderson pilot study five years ago, then her ovaries at 40. Cancer, mostly breast and ovarian, has been diagnosed at least seven times in her family, beginning with her grandmother’s generation.

“I was pretty nervous about the mutation, both the cancer risk and the idea of having my ovaries out even though I felt normal, healthy,” said Starr, a Houston surgical nurse.

“Being able to just have my tubes out initially was great,” she said. “It gave me a good feeling that I’d done something to protect myself without having to sacrifice anything.”

todd.ackerman@chron.com

twitter.com/chronmed

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It would be helpful if you linked to the articles/studies... Sx

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Many thanks

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The latest research shows no medical benefits to preventative surgery under the age of 60. It does highlight other potential problems instead. I would do some serious research personally before hand

Good luck

LA xx

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Between the 6 1/2 year time lag from Pre-cancer Fallopian tissue and the occurrence of OvCa, it may take a 7 to 10 year study to show the drop in new cancer cases.

The evidence is solid that Fallopian tissue is responsible for 75% of the 60 types of Ovarian cancer.

So if the tubes are removed after child bearing, there should be a decline of Ovarian cancer cases 7 to 30+ years down the road.

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Very interesting Rachael. Knowledge is good!! This may open up the possibility of trials for you in the future? I hope your daughter is negative but at least if she has the information she can make an informed decision regarding preventative surgery.

I am BRCA 1 positive and so is my eldest daughter. She is 37 and due to have her second (and almost certainly last) baby in September. She lives in Italy and the protocol there is to have the fallopian tubes removed as soon as possible after finishing your family and at 10 years younger than the age of the youngest relative at the point they were diagnosed with ovarian. My cousin was 50 (I was 53) so that means surgery by the age of 40, for my daughter. Removing only the fallopian tubes avoids all the problems linked with early menapause (for e.g heart desease) caused by removing the ovaries. She will then have her ovaries removed later -closer to natural menapause age. I think this is the way to go and is the case in some other European countries. As D Beavers says, research shows that the majority of ovarian cancers actually start in the fallopian tubes. In fact, my other cousin had preventative surgery at 53 (tubes and ovaries) and early stage cancer was found in her fallopian tubes! She therefore had full surgery and follow up chemo. Thankfully she has been desease free since. Any has its risks but you have to weigh up those risks and in my family's case this is a no brainer!

Liz

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My history starts the same as your 53 year old cousin, early stage cancer, found by chance, in one Fallopian tube when I was 58 and I had everything removed, which is normal procedure in the Netherlands. But 8 years later I am on my 5th line of chemo so we are all different.

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Hope you are doing ok Georgina, I'm going to be starting 4th line next month. Sorry, but I'm a bit confused, was it you or your cousin who they found desease in the fallopian tube? If your cousin did she have preventative surgery after your diagnosis? X

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It was me who was diagnosed Stage 1a in 2010. I was living in the Netherlands at the time and was fortunate to have the full preventative surgery including removing the oventum within weeks. They also followed it up with chemo so really I had a fighting chance of a full recovery. Your cousin has different genes and was saved by being proactive. It recurred within 18 months and the rest is history, although recurrence has always been in the abdominal area and the vital organs have remained untouched luckily so I too have some positive genes!

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Hi mummy bear, I find it SO interesting that most OC starts in the Fallopian tubes (mine did). It seems this isn't discussed that much. It seems Italy is way ahead of us in doing preventive salpingectomy, if there is a FH. Perhaps this is something we (or others) should/could campaign about? What do you think? Linda x

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Linda. I was a bit unsure at first when Sarah told me that they only take out the tubes but it makes complete sense to do that when you've finished your family and then you can decide about the ovaries a bit later. At her recent maternity appointment (her second child is due in September) they even said that if she needed a cesarean section (she did with her first due to placenta problems) and if she was sure they had completed their family, they could remove the tubes a the same time! X

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P.s I'm not a very good 'campaigner' I'm afraid but it definitely is interesting. I think eventually this will be adopted here but nothing happens fast on the NHS!

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MB, I find this fascinating as I was a midwife & have been present at many a Caesarean Section! So proactive - well done Italy! I will try to look into it all a bit more. Thanks again for such interesting info. Linda xx

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I'm not 100% sure this is the practice for the whole of Italy but Sarah lives in the mountains in the Trentino area and they have an extremely good reputation in oncology and gynecology. Hopefully she won't need a caesar but if she does it would be good to kill two birds with one stone!! Can't see that happening on the NHS, it would take too much organising!! Liz x

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Kudos to Italian medical protocol. I hope they do a comprehensive study to show the certain drop in cases of OvCa seven years after the surgery.

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I think it is only with BRCA positive as it was when Sarah mentioned this to them when she was pregnant the first time, that they brought the option up. They told her that the research showed that most Ovarian cancers start in the fallopian tubes and it was standard pratice therefore to (initially at least) remove only them. As she has diabetes and therefore has a higher chance of developing heart disease, leaving the ovaries in place until closer to natural menopause is a good decision.

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My mother died of OC in 2005 and I dont think Genetic testing was ever discussed. I had my ovaries removed in 2010 as i wanted to eliminate anything that would prevent me looking after my dad. I was diagnosed with stage 3 high Peritoneal cancer in Nov 2016 which is the same gene as OC. My consultant was concerned that i did not have my fallopian tubes removed at the same time. I finished my 18 sessions of Avastin in January and my CT scan showed that it had reoccurred so they put me back on carboplatin/caelex monthly and had my second one yesterday. I am gutted that i never got to have a break!! Still got to stay positive.

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Oh Angie it's crazy that you had preventative surgery and they left in the fallopian tubes!! I have had two recurrences to date (last one was carbo/caelyx and i responded very well) and will be back on chemo for a fourth time next month but i feel well and intend to be around for a long time yet!! Sending love and positity for a good response for you also. X

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I've just heard from Kate that she had a 'funny turn' on the way home from the hospital, and has broken her wrist. I think she should be tested for the 'coming over all of a doodah at the sight of a needle' gene. I blame her father. Have suggested counselling.

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Hi Rachael,

My mom was blind-sided at her diagnosis this past July for OC. We all were, it was out of nowhere because we've never had cancer in the family. After genetic testing, they also found the BRIP1 gene mutation. A surprise! Anyway, it is a strange shock because no one else in her family has ever had it. Now I need to get genetic testing on March 16h. The geneticist explained to us some of the numbers around the probability of also getting OC. What we learned is, if her offspring (myself) is also positive for BRIP1, there is just a 6% chance of ever getting ovarian cancer as well. I find that interesting and tough as I too will need to think about what to do if I end up carrying the gene as well. A 6% chance is very small but at the same time it's still a chance. I never thought I'd have to go through these decisions. And, I too wish they had more info and research on this BRIP1 gene! Good luck with your daughter, and good luck to you on your journey.

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Hi Rachael47. I am pretty new on this site. Glad you shared your genetic info. In 2015 I was diagnosed at stage 3 Oc. After surgery and chemo I went for the testing and all came back negative. So I was classified as "environmental" since I had no mutations. In February as a 3 mos CA125 test my numbers. Went up to 22 from 11 which sent up a red flag. Catscan revealed I had a spot near my liver so I'm back for chemo. My dr said they now have a way of going back to my tumor specimen to see if it had developed any mutations. Something they did not know hey could do just 3 yrs ago. I'm not sure what happens from there. I guess my long winded response here is that, hopefully, your daughter's test doesn't necessarily mean she should have anything removed. I guess it's just enough that the insurance company will now cover the costs of monitoring and stay on top of it.

I hope in some way this helps. Sometimes the genetic test tells you what you are carrying but not nessarily that it will happen.

Wishing you and your daughter the very best. Thank God that today we have ways of detecting all this and just challenge this cancer thing into a tiny corner.

Marisa

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It's the distinction between germ-line - in your body make-up all the time, and somatic - in the tumour.

I've had both tested. Like you I had no germ-line mutations, but the tumour did have some: a couple of very common ones and others of "unknown significance".

Given how research is progressing this can be useful info to have as potentially, in the future, treatment can be more targeted, rather than the one size fits all model we tend to start off with currently. There are lots of clinical trials around.

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Thank you for this explanation Mac27-UK.

I was confused when the Dr. said that they needed my permission to go back in and test my tumor they had removed so as to see if it had any mutations. I thought since I was negative in the Genetic testing that it couldn't be a result of that, so, apparently it is.

So you are saying, that, based on them able to target the mutation, they may be able to come up with a targeted treatment? That sounds pretty encouraging. Thank you so much.

Marisa

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