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All TopicsForum: Not Diagnosed With a Recurrence or Metastases but Concerned → Topic: Will 30% of Early Stage (1-IIIA) go on to metastasize??

Topic: Will 30% of Early Stage (1-IIIA) go on to metastasize??

Forum: Not Diagnosed With a Recurrence or Metastases but Concerned —

Meet others concerned about developing a recurrence or metastases.

Posted on: Oct 15, 2013 12:16PM - edited Nov 12, 2013 12:49PM by SusansGarden

SusansGarden wrote:

So I started this question in another thread but was hoping for additional feedback.

With MBC awareness day last weekend, a stat is going around that caught my attention. Basically says that 30% of early stage BC patients will eventually have their bc metastasize AFTER adjuvant treatment. Susan G. Komen even states it here --> Click Here

So I feel like I've researched the hell out of BC since my diagnosis in 2010 and have never heard/noticed that stat before. I'm thinking...oh that must be some sort of average through stage 3, and certainly wouldn't be very relevant for Stage 1?

But then somebody kindly directed me to this link --- > Click Here

According to the link it states (my bold):

"Quote from The Oncologist Journal “Prognostic and Predictive Factors in Early-Stage Breast Cancer” (May 2004) “The poor outcome with the Halstedian approach, as well as the observation that 20%-30% of node-negative patients ultimately develop metastatic disease, led to the currently held micrometastatic paradigm. This paradigm asserts that many patients with early-stage disease have distant micrometastatic disease present at the time of diagnosis, putting them at risk for the later development of overt metastatic disease."

So "node negative" would clearly mostly include Stage I. So it is saying that 20-30% of stage ONE bc patients will metastasize? That's certainly not what the oncs or cancer math tell you. Though looking at cancermath it only gives you stats for 15 year survival. It's not telling you your percentage of never having BC again in your life.

The link says "Statistics are not collected for metastatic recurrences which comprise the larger portion of mbc cases. Statistics are only gathered for initial diagnosis of Stage IV metastatic disease."

WTH? I can't believe they don't track how many original BC's end up metastasizing? I would think that would be valuable information. If the 20-30% really is true, I think it definitely should be more publicized. Instead of this widely advertised stat of 98% survival rate. (when it's only talking 5 years). Shoot, I think a lot of Stage IV bc's are outliving 5 years.

None of this changes what I would/did do for treatment (I think! - now I'm wondering about the 10 yrs instead of 5 on tamox). I'm pretty much of the mindset that you do what you can with the knowledge, advice and resources that you have at the time and then try not to worry about it. It's out of your hands at that point. But I would like to know the true stats of how many bc's come back no matter what the hell we do for treatment. I'm sure it will probably scare the hell out of some people, but it would also get more people demanding more money goes towards a cure than this pink sugar coated misleading happy wappy "nobody dies of bc anymore" crap. I don't know. What do you all think? I was lead to believe that I had a 90%+ chance of never seeing bc again, when it really could be 70 to 80%? Does it matter at this point? Are we better off not knowing? Or is knowledge power in this case?

*****Edited to add: *******Momine (on page 6) added this ~ "I tracked down that 30% thing, because it just didn't sound right. The statement is attributed to Dr. Iman Mohamed, a breast cancer specialist. I tweeted her to ask what this number means. She kindly responded that this is the average recurrence of all breast cancers if not treated with systemic therapy (chemo, tamox, AI)."

So that is certainly reassuring news for early stagers, however, should not diminish the fact that we need a cure and better treatments for Stage IV. And the media needs to stop with the scare tactics and misleading statistics to the general public.

Edited AGAIN ... Despite Momine's reassuring statement from Dr. Iman Mohamed... I'm still finding crap on the internet saying similiar stats even AFTER treatment... not w/out treatment. (See page 8) And the conversation continues....... :)

"If you want to forget all your other troubles, wear too tight shoes." Dx 10/6/2010, IDC, 1cm, Stage IA, Grade 2, 0/3 nodes, ER+/PR+, HER2- Surgery 11/30/2010 Mastectomy: Left; Prophylactic mastectomy: Right; Reconstruction (left): Tissue expander placement; Reconstruction (right): Tissue expander placement Hormonal Therapy 2/1/2011 Surgery 7/10/2013 Prophylactic ovary removal
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Jan 9, 2018 12:24PM Paco wrote:

Hmm, statistics. There are so many factors involved in breast cancer that it becomes very hard to glean any real truths from these numbers.

For all stages combined, the 5-year survival for female breast cancer is 90% and on average, 80% of people diagnosed with breast cancer live for 10 years or longer. We might also want to consider that the median and mean age for being diagnosed with breast cancer is 62, so half of women diagnosed are older and half are younger than that number. The average life expectancy of a woman in the United States is 81. So I suppose if you are diagnosed above the age of 62, as half of women diagnosed are, you can live a very full and normal life with a 15- or 20-year survival. My husband's grandmother was diagnosed at the age of 80 and lived to be 88 years old. She would make our survival statistics look bad but leaving this world at 88 sounds pretty good right now.

I would read the statistics that that many, many women living with a breast cancer diagnosis will actually live long and productive lives.

Dx @ 48 Dx 12/28/2017, DCIS, Right, 1cm, Stage 0, Grade 2, ER+/PR+ Surgery 2/13/2018 Lumpectomy: Right Radiation Therapy 3/27/2018 Whole-breast: Breast Hormonal Therapy 4/25/2018 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
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Jan 23, 2018 08:19AM NicolaSue wrote:

Kelly ,

The basic fact is that more BCs are being discovered earlier and that makes it difficult to know what the real stats are because a decade ago people were often diagnosed when the disease was more advanced. Take me for example with 'only' LCIS. Most LCIS even now is only picked up when you are investigated for something else. But I have LCIS and just LCIS and there will be many more like me picked up with BC stage zero due to enhanced surveillance.

When I was first diagnosed I got hung up on the stats - then I decided that as I couldn't change the stats it would be better to use my time and energy on trying to keep healthy. I'm finding that hard work enough!

If I'm reading your signature right I think you are due surgery soon. Good luck!

LCIS diagnosed Spring 2017. Vacuum excision biopsy. First follow up mammo 2018 - clear
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Jan 26, 2018 02:08PM Molly50 wrote:

This is interesting: Long-term breast cancer recurrence risk linked to original TN status


13-11-2017 | Hormone-receptor positive breast cancer | News

Long-term breast cancer recurrence risk linked to original TN status

medwireNews: The risk for breast cancer recurrence increases at a steady rate for at least 15 years after the end of planned endocrine therapy and is strongly associated with the original tumor diameter and nodal (TN) status, meta-analysis data show.

The findings are based on the results of 88 trials involving 62,923 women with early-stage estrogen receptor (ER)-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy.

Hongchao Pan (University of Oxford, UK) and co-investigators from the Early Breast Cancer Trialists' Collaborative Group say the results have "implications for long-term follow-up strategies and [highlight] the need for new approaches to reduce late recurrence."

"The risk could be somewhat reduced by extending the duration of endocrine therapy, with greater absolute benefits for those at highest risk for recurrence," they add.

The researchers report in The New England Journal of Medicine that patients with stage T1 disease and no nodal involvement (T1N0) had a 13% cumulative risk for distant recurrence at 20 years. This increased to 20% with one to three nodes involved (T1N1–3), and 34% with four to nine nodes involved (T1N4–9).

The corresponding risks among women initially diagnosed with stage T2 disease were 19% with T2N0, 26% with T2N1–3, and 41% with T2N4–9.

Similar results were observed for the risk for death from breast cancer, but there was no association between TN status and the risk for contralateral breast cancer, the researchers remark.

The team also found that tumor grade and the presence of Ki-67 antibody (which were strongly correlated with each other) only moderately predicted long-term outcome, despite being important independent prognostic factors during the first 5 years.

Progesterone receptor and human epidermal growth factor receptor type 2 receptor status also predicted outcome during the first 5 years, but had no impact on long-term prognosis.

When Pan et al further divided the patients according to tumor grade, they found that, among patients with T1N0 breast cancer, the absolute risk for distant recurrence during years 5 to 20 was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease.

The corresponding risks for any recurrence or a contralateral breast cancer were 17%, 22%, and 26%, respectively.

The study authors conclude: "Recognition of the magnitude of the long-term risks of ER-positive disease can help women and their health care professionals decide whether to extend therapy beyond 5 years and whether to persist if adverse events occur."

By Laura Cowen

54 years old. Chek2 mutation. Family history of BC. Oncotype Dx 13 Extensive LVI Dx 6/8/2015, IDC, Left, 2cm, Stage IIB, Grade 2, 2/9 nodes, ER+/PR+, HER2- (FISH) Dx 7/29/2015, DCIS, Left, <1cm, Stage 0, Grade 2, ER+/PR+ Surgery 7/29/2015 Lumpectomy: Left; Lymph node removal: Underarm/Axillary Surgery 9/4/2015 Mastectomy: Left; Reconstruction (left): Tissue expander placement Hormonal Therapy 10/13/2015 Arimidex (anastrozole) Radiation Therapy 10/20/2015 Whole-breast: Breast, Lymph nodes, Chest wall Hormonal Therapy 4/22/2016 Aromasin (exemestane) Surgery 7/22/2016 Prophylactic mastectomy: Right; Reconstruction (right): Tissue expander placement Surgery 3/21/2017 Reconstruction (left): Silicone implant; Reconstruction (right): Silicone implant
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Jan 26, 2018 02:16PM - edited Mar 10, 2018 01:23PM by BarredOwl

This Post was deleted by BarredOwl.
Stage IA IDC, 9/2013 BMX. Right: IDC (1.5 mm, grade 2) with DCIS (5+ cm), 0/4 nodes, pN0. Left: DCIS (5+ cm), 0/1 node, pN0(i+).
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Jan 27, 2018 10:59AM Outfield wrote:

Kellyoc, the problem with looking at it that way is that you lump a group of very diverse diseases together so for any particular individual, the analysis is useless.

For example, think of a different disease: Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (TEN). A lot of people have never heard of it, but it's pretty easy to understand. Usually as a response to an drug, the top part of the skin detaches and people get huge blisters. When those unroof, it's like having a serious burn. If it involves less than 10% of the body surface area, it's called SJS; more than 30% it's called TEN, 10-30% is considered "overlap," but it's all the same disease, just different degrees of severity. The fatality rate for SJS is roughly 5%, TEN is at least 20%. SJS is much more common; this isn't the exact number, but for easy statistics let's say 9:1. Take 200 patients: 180 of whom have a 5% risk of dying = 9 total, 20 who have a 20% risk == 4 total. Add them all together, 13 of 200 expected to die, = 6.5%.

Do you see how the risk associated with the more common, less serious range of the disease statistically overwhelms the more serious type? The family of a person with TEN covering 70% of their body would be sadly misled if told the risk of death is 6.5%.

In an analogous way, lumping all breast cancer together (the "combined" thing) helps nobody. Breast cancer is too diverse a disease, especially if DCIS is included. Many women with early stage disease have a great prognosis and a tiny chance of recurrence, but someone like me has a >40% chance of recurrence (20 years for me would be age 64, time that I'm hoping to be part of the prime of my life).

To lump us all together minimizes how serious and life-threatening more advanced breast cancer actually is. In the worst case, it perpetuates a popular misconception that the disease is trivial.


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Jan 28, 2018 02:44AM Momine wrote:

41% with T2N4–9 (risk of recurrence over 20 years), taken above from Molly50's post. That would be me. Thing is, 20 years from DX I will be 69. Still "young" but not exactly a kid. So far I am 6 years out, and I have lived well the last 6 years. I make a serious effort to live in such a way that I can die at any time without deep regrets. I intend to continue doing so for however long I get. In the end, it makes no sense to ruin your life by ruminating on the prospect of dying, whatever your odds are.

Furthermore, I deliberately went for the most aggressive treatment possible at the time of my DX. My thinking was that research rolls on, however slowly, and the longer I can stave off a recurrence, the better the chances that some new treatment shows up in the meanwhile.

Lastly, as discouraging as that 41% stat is, I still have better than a 50/50 chance :D

Dx 6/1/2011, ILC, 5cm, Stage IIIB, Grade 2, 7/23 nodes, ER+/PR+, HER2- Chemotherapy 6/20/2011 Cytoxan (cyclophosphamide), Ellence (epirubicin), Fluorouracil (5-fluorouracil, 5-FU, Adrucil), Taxotere (docetaxel) Surgery 9/13/2011 Mastectomy: Left, Right Radiation Therapy 1/9/2012 Surgery 3/8/2012 Prophylactic ovary removal Hormonal Therapy 4/1/2012 Femara (letrozole)
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Jan 29, 2018 03:42PM marijen wrote:

Good News, Bad News on Breast Cancer Survival Rate

More women are surviving breast cancer, but more than 40,000 will still die from the disease this year. Living with it hasn't gotten much easier, either.

Early detection and better treatments helped prevent 322,000 breast cancer deaths between 1989 and 2015.

A new American Cancer Society (ACS) report shows that the breast cancer death rate decreased by 39 percent during those years.

It's encouraging news.

But breast cancer remains a significant health problem.

It's second only to lung cancer as the leading cause of cancer deaths among women in the United States.

The disease affects women and men of all ages.

About 81 percent of diagnoses occur in women aged 50 and up. About 89 percent of breast cancer deaths also occur in this age group.

The ACS estimates there'll be more than 252,000 new cases of invasive breast cancer in women this year.

And more than 40,000 will die of the disease.

Stubborn disparities

Dr. John A. P. Rimmer, a breast cancer surgeon in Florida, told Healthline that a number of factors working together for the past 30 years contributed to the improved survival rate.

Among them are better diagnostic tools and surgical techniques, as well as newer chemotherapy regimens and targeted therapies.

The ACS report notes that not all women have benefited from these improvements.

The overall incidence rate was 2 percent lower in non-Hispanic black women, compared to non-Hispanic white women.

But from 2011 through 2015, the death rate was 42 percent higher in black women. This is a small improvement from 2011, when it was 44 percent higher.

The lowest incidence and death rates are among Asian and Pacific Islander women.

The report indicates that biologic, social, and structural factors all contribute to these disparities.

These include stage at diagnosis, other health issues, and access and adherence to treatment.

Also, black women have a higher rate of triple-negative breast cancer, a particularly aggressive form of the disease.

Disparities vary from state to state. Access to healthcare is still a problem.

"Breast cancer is very complex socially and emotionally," said Rimmer.

In his practice, Rimmer has seen women who skipped screening or didn't initially seek medical care due to lack of health insurance.

Delayed diagnosis and treatment affects chances of survival.

Others refuse all or part of treatment due to cultural differences or misconceptions. And there are some who choose nonconventional treatments that simply don't work.

Rimmer said that people aren't always forthcoming about the reasons why they don't show up for treatment.

What it's like to live with breast cancer

At the start of 2016, there were more than 3.5 million breast cancer survivors in the United States.

"If we treat you and you're alive, it's a good thing. But there's nothing good about breast cancer," said Rimmer.

He added that survivors often experience long-term consequences of chemotherapy, surgery, and radiation treatments.

Laura Holmes Haddad, author of "This Is Cancer," is one of those survivors.

The California mother of two received a diagnosis of stage 4 inflammatory breast cancer in 2012.

She was 37 years old.

To say her life changed would be an understatement.

"When I look back, I think about how naïve I was. The things I thought would be the hardest, like being bald, were actually the easiest for me. But the things I thought I would breeze through, like having both breasts removed and having breast reconstruction, were the hardest," Haddad told Healthline.

"Physically, I faced pain and discomfort and physical changes I couldn't have imagined," she continued.

Haddad lists nerve pain, nausea, sensory issues, and being bedridden among the physical side effects of treatment.

Then there's the mental and emotional toll.

"I felt angry and bitter at first, and sad. And then I felt guilty and helpless. And I tried to feel hopeful and I tried to laugh when I could, because everything just gets so absurd that you just have to laugh to relieve the darkness. I felt lonely and isolated, and that was tough. And then I felt grief and then I finally hit acceptance. And that felt good," explained Haddad.

For her family, it was a month after month marathon of logistical and emotional challenges.

Her husband helped as much as he could. But he also had to continue working to keep up with health insurance and mounting cancer-related expenses.

To get through it all, they relied on help from their extended family, friends, and community.

A new normal

"I still have nerve pain in my chest and discomfort, so it is hard to ever completely forget what you have been through," said Haddad.

She still sees her oncologist every three months. She'll need to take estrogen blockers for the rest of her life.

"Because I am BRCA2-positive, I have a higher risk of developing melanoma, especially after the extensive radiation treatment I had," she added.

That means seeing a dermatologist every three months and avoiding the sun as much as possible.

"I also have to keep my weight at a healthy level to lessen the risk of recurrence. Finally, I have to watch for lymphedema in my left arm because I had 14 lymph nodes removed. I also received radiation on my left side, leaving a high risk for developing lymphedema. I see a physical therapist and do daily arm exercises for that," she continued.

Haddad's pet peeve is that people often think of breast reconstruction after mastectomy as a "boob job."

"I can't tell you how many times people told me that at least I'd have a new pair of boobs at the end of it. I tried to smile and joke about it, but in the end, my bilateral mastectomy was one of the hardest aspects of having breast cancer. I will never, ever forget the day the bandages around my chest were unwound in the surgeon's office, a few days after the surgery," she said.

"But after all those challenges, I can tell you one thing. I do not take one second for granted. I really do try and pay attention to every moment, every interaction, every bird I see, every conversation I have. There is no time to waste on nonsense. And I wouldn't trade that," Haddad said.

Research is key

"Cancer cells are nasty and sophisticated," said Rimmer. "The amount of knowledge we have is huge, but the cellular mechanism is hugely complex."

He emphasized that breast cancer isn't a single disease. Some types are more aggressive than others.

He believes research is one way to keep the death rate on the decline, especially when it comes to targeted therapies for the most aggressive types of breast cancer. He also said it's important to identify high-risk women, such as those with BRCA gene mutations.

"At the other end of the spectrum, just simple things like getting a mammogram or going to the doctor when you have a lump are beneficial. Prevention is better than a cure," Rimmer said.

Clinical trials are crucial to developing new treatments.

Haddad took part in a clinical trial for the drug veliparib. She credits it with shrinking her tumor enough for surgery.

There are challenges to participating in trials, even if your health insurance covers all or part of the treatment.

For Haddad, that meant weekly plane fares, hotel nights, and other travel-related expenses.

"No one really tells you about the logistics of navigating all that while on chemotherapy," she said.

But she believes that funding research and encouraging people with cancer to participate in clinical trials is important.

Many people don't realize that breast cancer can still be deadly, according to Haddad.

"I also don't think they realize — I certainly didn't — how important medical research is in developing treatment options and hopefully one day a cure for breast cancer," she said.

Www.healthline.com


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Jan 29, 2018 03:49PM - edited Jan 29, 2018 03:55PM by marijen

This Post was deleted by marijen.
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Jan 29, 2018 08:10PM - edited Jan 29, 2018 08:25PM by stephaniebc

i manage my fear of recurrence with meditation and -- although it may sound counter-intuitive -- by making a conscious effort to think about death a little bit every day, to get acquainted with it, so to speak, so that it's not so scary. the stage IV threads are very inspiring to me in that respect.

death is truly a taboo subject in our culture and i feel a little bit more enlightened now.

Dx 11/2016, IDC, 2cm, Stage IIA, Grade 3, ER+/PR+, HER2+ Chemotherapy 12/13/2016 AC + T (Taxol) Targeted Therapy 3/16/2017 Perjeta (pertuzumab) Targeted Therapy 3/16/2017 Herceptin (trastuzumab) Surgery Lumpectomy: Right; Lymph node removal: Sentinel
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Jan 29, 2018 08:12PM stephaniebc wrote:

ps- this doesn't mean that i am fatalistic, of course. i do all the things, the eating well, the turmeric, the exercise and whatnot.

Dx 11/2016, IDC, 2cm, Stage IIA, Grade 3, ER+/PR+, HER2+ Chemotherapy 12/13/2016 AC + T (Taxol) Targeted Therapy 3/16/2017 Perjeta (pertuzumab) Targeted Therapy 3/16/2017 Herceptin (trastuzumab) Surgery Lumpectomy: Right; Lymph node removal: Sentinel
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Jan 29, 2018 08:41PM Rosabella wrote:

heart disease is higher deaths than bc.

Dx 6/2/2015, IDC, Left, 6cm+, Stage IIIA, Grade 3, 1/4 nodes, PR+, HER2- Surgery 8/6/2015 Lymph node removal: Left, Sentinel, Underarm/Axillary; Mastectomy: Left, Right; Reconstruction (left): Silicone implant; Reconstruction (right): Silicone implant Chemotherapy 11/3/2015 AC + T (Taxotere) Radiation Therapy 5/4/2016 Whole-breast: Breast, Lymph nodes Hormonal Therapy 6/28/2016 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Targeted Therapy
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Jan 30, 2018 02:17AM Momine wrote:

Stephanie, same here. Coming to terms with death has helped me live.

Dx 6/1/2011, ILC, 5cm, Stage IIIB, Grade 2, 7/23 nodes, ER+/PR+, HER2- Chemotherapy 6/20/2011 Cytoxan (cyclophosphamide), Ellence (epirubicin), Fluorouracil (5-fluorouracil, 5-FU, Adrucil), Taxotere (docetaxel) Surgery 9/13/2011 Mastectomy: Left, Right Radiation Therapy 1/9/2012 Surgery 3/8/2012 Prophylactic ovary removal Hormonal Therapy 4/1/2012 Femara (letrozole)
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Feb 3, 2018 12:09PM marijen wrote:

GATA-3 Expression as a Predictor of Hormone Response in Breast Cancer Purvi Parikh, MD, Juan P. Palazzo, MDLewis J. Rose, MD Constantine Daskalakis, SCDRonald J. Weigel, MD, PhD (FACS)'Correspondence information about the author MD, PhD Ronald J. WeigelPlumX Metrics

DOI: https://doi.org/10.1016/j.jamcollsurg.2004.12.025

Background

Expression of estrogen receptor-α (ERα) as determined by immunohistochemistry of tumor tissue is currently the most clinically useful test to predict hormone responsiveness of breast cancer. Thirty percent of ERα-positive breast cancers do not respond to hormonal therapy. GATA-3 is a transcription factor that is expressed in association with ERα and there is evidence that GATA factors influence response to estrogen. In this pilot study, we investigated whether GATA-3 expression is associated with hormone response in breast cancer.

Study design

Breast cancer tissue was stained for GATA-3 expression by immunohistochemistry in ERα-positive cancers from 28 patients, 14 of whom were defined as hormone unresponsive (cases) and 14 of whom were age-matched controls with hormone-responsive, ERα-positive cancers (controls).

Results

Comparing cases and controls, there were no differences in expression of ERα; progesterone receptor, ErbB2; or tumor grade. Using 20% nuclear staining to characterize tumors as GATA-3 positive or GATA-3 negative, 6 of 14 (43%) cancers in the hormone-unresponsive group and none of the controls were classified as GATA-3 negative (odds ratio, 8.2; 95% confidence interval, 1.2−∞; p = 0.031). Using different cut points to characterize GATA-3 positivity yielded very similar results, indicating a positive association between lack of GATA-3 expression and lack of response to hormonal therapy.

Conclusions

The study suggests that analyzing ERα-positive breast tumors for GATA-3 using immunohistochemistry might improve prediction of hormone responsiveness. The association between GATA-3 expression and hormone response suggests that GATA-3 may play a role in mechanisms controlling response to estrogen.

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Feb 5, 2018 11:36AM jojo9999 wrote:

Does anyone know if GATA-3 is part of thhe Breast Cancer Index? (BCI)?

Dx 8/2014, ILC, Right, 1cm, Stage IIA, Grade 1, 1/4 nodes, ER+/PR+, HER2- (DUAL) Surgery 9/8/2014 Mastectomy: Left, Right; Reconstruction (left); Reconstruction (right) Radiation Therapy 11/11/2014 Hormonal Therapy 12/22/2014 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
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Feb 12, 2018 08:59AM marijen wrote:

Researchers identify presence of ER gene fusion proteins in treatment-resistant breast cancer February 7, 2018

At Magee-Womens Research Institute (MWRI) and UPMC Hillman Cancer Center, a large team of clinical and laboratory researchers dedicated to understanding treatment resistance in the most common form of breast cancer have identified a new genetic change in the estrogen receptor (ER) that contributes to therapy resistance. ER-positive breast cancer, diagnosed in two-thirds of breast cancer patients, is fueled by the presence of estrogen in the body. Anti-estrogen therapy is usually successful in treating the disease initially, but ER-positive breast cancers will often recur because tumors develop a resistance to treatment.

Published in the Annals of Oncology, the research identifies the presence of ER gene (ESR1) fusion proteins in treatment-resistant breast cancer. This is the first time that recurrent ESR1 fusion proteins have been identified in human breast cancer, and understanding how they function could lead to improved treatments for the disease.

Related Stories

"We first identified this change in a patient who had ER-positive breast cancer, received anti-estrogen therapy, had her breast cancer recur and eventually passed away from the disease," said senior author Adrian Lee, Ph.D., director of the Women's Cancer Research Center at MWRI and UPMC Hillman Cancer Center, and professor of Pharmacology & Chemical Biology at the University of Pittsburgh. "A member of our lab noticed the mutation while performing posthumous genetic analysis from tissue in our organ donation program, and over time we were able to identify many more cases of this mutation in patients with recurrent disease." This work was performed in collaboration with Foundation Medicine Inc., a genomic testing company that examined ESR1 fusions in close to 10,000 breast cancers sequenced with the FoundationOne CDx test.

According to Lee, ESR1 fusion proteins "outsmart" traditional treatment by splitting in half and eliminating the binding site that anti-estrogen therapy targets.

"Physicians will continue administering anti-estrogen therapy, not realizing this genetic mutation has occurred," said Lee. "Now that we understand the change, though, we can detect it with a blood test and help improve treatments for this form of the disease."

According to Lee, genetic analysis will soon be the dominant field of ER-positive breast cancer research, eventually leading to improved treatments and patient outcomes.

"Genomic sequencing is telling us so much about breast cancer. I believe the research we are doing in the laboratory will have a significant clinical impact in the near future, and the work we are doing will play a large part in improving patient care and survival," said Lee.

Source:

http://www.upmc.com/media/NewsReleases/2018/Pages/lee-breast-cancer-treatment.aspx

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Feb 12, 2018 01:49PM Lisey wrote:

Marijen, Is that related to this? https://www.nature.com/articles/cr201815

Oncotype =20, ER 95%, PR 5%, ki67= 30%, Mammoprint = Low, Blueprint = Luminal A!!!! TEs= Iron Bra of Death - not worth all the complications for foobs that I'll never feel. Flat and fealess now. Dx 5/11/2016, IDC, Right, 1cm, Stage IA, Grade 2, 0/6 nodes, ER+/PR+, HER2- Surgery 6/1/2016 Lymph node removal: Sentinel Surgery 6/14/2016 Mastectomy: Left, Right; Reconstruction (left): Tissue expander placement; Reconstruction (right): Tissue expander placement Surgery 7/6/2016 Mastectomy: Left, Right Hormonal Therapy 7/14/2016 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
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Feb 12, 2018 01:52PM Lisey wrote:

I'm hoping someone like BarredOwl will talk me off the walls after i read this article. It appears 2/3rds of us have this variation. ugh.

Tamoxifen enhances stemness and promotes metastasis of ERα36+ breast cancer by upregulating ALDH1A1 in cancer cells

"The 66 kDa estrogen receptor alpha (ERα66) is the main molecular target for endocrine therapy such as tamoxifen treatment. However, many patients develop resistance with unclear mechanisms. In a large cohort study of breast cancer patients who underwent surgery followed by tamoxifen treatment, we demonstrate that ERα36, a variant of ERα66, correlates with poor prognosis. Mechanistically, tamoxifen directly binds and activates ERα36 to enhance the stemness and metastasis of breast cancer cells via transcriptional stimulation of aldehyde dehydrogenase 1A1 (ALDH1A1). Consistently, the tamoxifen-induced stemness and metastasis can be attenuated by either ALDH1 inhibitors or a specific ERα36 antibody. Thus, tamoxifen acts as an agonist on ERα36 in breast cancer cells, which accounts for hormone therapy resistance and metastasis of breast cancer. Our study not only reveals ERα36 as a stratifying marker for endocrine therapy but also provides a promising therapeutic avenue for tamoxifen-resistant breast cancer."

Oncotype =20, ER 95%, PR 5%, ki67= 30%, Mammoprint = Low, Blueprint = Luminal A!!!! TEs= Iron Bra of Death - not worth all the complications for foobs that I'll never feel. Flat and fealess now. Dx 5/11/2016, IDC, Right, 1cm, Stage IA, Grade 2, 0/6 nodes, ER+/PR+, HER2- Surgery 6/1/2016 Lymph node removal: Sentinel Surgery 6/14/2016 Mastectomy: Left, Right; Reconstruction (left): Tissue expander placement; Reconstruction (right): Tissue expander placement Surgery 7/6/2016 Mastectomy: Left, Right Hormonal Therapy 7/14/2016 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
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Feb 12, 2018 02:09PM KBeee wrote:

The science nerd in me is intrigued. Hoping they find a simple way to test for this so they know who should start with an AI and skip Tamoxifen. Having failed on Tamoxifen rather quickly, I found this interesting.

I did not catch the 2/3 number in the article, but I did not red every word of it; I skimmed a few parts that were a bit over my head.

Karen. Dx 8/5/2013, IDC, Right, 1cm, Grade 2, 0/1 nodes, ER+/PR+, HER2- (IHC) Surgery 8/25/2013 Mastectomy: Left, Right Chemotherapy 9/19/2013 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Hormonal Therapy 12/11/2013 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Surgery 1/22/2014 Reconstruction (left); Reconstruction (right) Surgery 1/28/2015 Lumpectomy: Right Dx 2/2/2015, IDC, Right, 1cm, Grade 2, 0/0 nodes, ER+/PR-, HER2- (FISH) Surgery 2/24/2015 Lumpectomy: Right; Lymph node removal: Right, Sentinel, Underarm/Axillary; Prophylactic ovary removal Dx 2/25/2015, IDC, Right, 1cm, Grade 3, 0/13 nodes, ER+/PR-, HER2- (IHC) Chemotherapy 3/30/2015 AC + T (Taxol) Radiation Therapy 8/24/2015 Whole-breast: Breast, Lymph nodes, Chest wall Hormonal Therapy Femara (letrozole)
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Feb 12, 2018 02:22PM Lisey wrote:

I used this to get the 2/3rds... The antibody was used to examine the expression of ERα36 in 1 677 human breast cancer samples from five independent cohorts. In the first cohort (Cohort Chongqing) of 1 068 cases, 734 (68.7%) breast cancer specimens were ERα66+ and 493 (46.2%) were ERα36+ Among 734 ERα66+ samples, 329 (44.8%) co-expressed ERα36. ERα36 was also detected in 164 of 334 (49.1%) ERα66− tumor specimens

1677 total and 1068 of those were ER+ cases:

46.2 were ER36+ from the study (493)..

among the 734 that were ER66+, 44.8% co expressed ER36+.(329)

among the ER-, there were half that expressed ER36+ as well: (164)..

so of the 1677 cases 964 were ER36+... = 57% or close to the 2/3rds I estimated.

Oncotype =20, ER 95%, PR 5%, ki67= 30%, Mammoprint = Low, Blueprint = Luminal A!!!! TEs= Iron Bra of Death - not worth all the complications for foobs that I'll never feel. Flat and fealess now. Dx 5/11/2016, IDC, Right, 1cm, Stage IA, Grade 2, 0/6 nodes, ER+/PR+, HER2- Surgery 6/1/2016 Lymph node removal: Sentinel Surgery 6/14/2016 Mastectomy: Left, Right; Reconstruction (left): Tissue expander placement; Reconstruction (right): Tissue expander placement Surgery 7/6/2016 Mastectomy: Left, Right Hormonal Therapy 7/14/2016 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
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Feb 12, 2018 02:45PM marijen wrote:

I would say it’s related Lisey. And it seems that Tamoxifen “activates” the ERa36? They better start testing for it. Yes, we need BarredOwl for this

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Feb 12, 2018 03:37PM - edited Feb 12, 2018 03:37PM by KBeee

It does seem like higher expression is the biggest problem. Hopefully it'll eventually be like HER2; they can measure if it's over expressed, and have a drug to target it. Hoping it comes in our lifetimes!

Karen. Dx 8/5/2013, IDC, Right, 1cm, Grade 2, 0/1 nodes, ER+/PR+, HER2- (IHC) Surgery 8/25/2013 Mastectomy: Left, Right Chemotherapy 9/19/2013 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Hormonal Therapy 12/11/2013 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Surgery 1/22/2014 Reconstruction (left); Reconstruction (right) Surgery 1/28/2015 Lumpectomy: Right Dx 2/2/2015, IDC, Right, 1cm, Grade 2, 0/0 nodes, ER+/PR-, HER2- (FISH) Surgery 2/24/2015 Lumpectomy: Right; Lymph node removal: Right, Sentinel, Underarm/Axillary; Prophylactic ovary removal Dx 2/25/2015, IDC, Right, 1cm, Grade 3, 0/13 nodes, ER+/PR-, HER2- (IHC) Chemotherapy 3/30/2015 AC + T (Taxol) Radiation Therapy 8/24/2015 Whole-breast: Breast, Lymph nodes, Chest wall Hormonal Therapy Femara (letrozole)
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Feb 12, 2018 04:47PM solfeo wrote:

I have been on the fence about when to upgrade to the "big girl meds" (what my stupid ex-oncologist calls AIs). I guess I probably will sooner rather than later. Tamoxifen resistance has always been a concern, plus I have the genetic polymorphism that means I don't properly metabolize tam to begin with. Seems like it would be a sure path to metastasis if I happened to have all of these problems combined, and we can't know when we aren't tested.
Oncotype 13 Dx 7/31/2015, IDC, Right, 3cm, Stage IIA, Grade 1, 0/2 nodes, ER+/PR+, HER2- (FISH) Surgery 10/7/2015 Lymph node removal: Right, Sentinel; Mastectomy: Left, Right Hormonal Therapy 11/17/2015 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
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Feb 12, 2018 05:38PM runor wrote:

Solfeo, when I read what your oncologist says, 'big girl meds', what a frickin asshole! Is this a joke to him? Are the side effects and the real concerns you have something for him to give pet names to? Oh my god, your big girl foot should kick him in his big boy ass!

I tell myself I am 'lucky' that tamoxifen offers me some hope. Because as much as I didn't want to do chemo, scared to death, I also felt that it was at least some sort of hunting party to actively KILL the dirty cancer. But no. No chemo for me. Chemo won't do me a lick of good. Take your tamoxifen and don't give it a second thought.

Well I do give it a second thought. The more I read the more I realize that tamoxifen has some pretty big holes in its protective shield. Right off the start some of us will never metabolize it. Then those of us who do metabolize it initially may, over time, develop a resistance to it. Oh joy.

The more I read this the more vulnerable and exposed I feel. Some days it's a battle to not feel like a sitting duck with a target on my back. I cannot say for sure but I don't think the Oncotype test looks into these genes. Maybe this test that we all placed our hopes in, holding onto those scores like lifelines, is going to go up in flames as not adequately covering the bases?

This calls for alcohol. Lots and lots of alcohol.

Dx 3/23/2017, IDC, Left, 2cm, Stage IIB, Grade 2, 0/1 nodes, ER+/PR+, HER2- Surgery 4/12/2017 Lumpectomy: Left; Lymph node removal: Sentinel Radiation Therapy 7/4/2017 Whole-breast: Breast Hormonal Therapy Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
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Feb 12, 2018 06:17PM - edited Mar 8, 2018 12:07PM by BarredOwl

This Post was deleted by BarredOwl.
Stage IA IDC, 9/2013 BMX. Right: IDC (1.5 mm, grade 2) with DCIS (5+ cm), 0/4 nodes, pN0. Left: DCIS (5+ cm), 0/1 node, pN0(i+).
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Feb 12, 2018 06:54PM Traveltext wrote:


Thanks BarredOwl. There are issues here for men, too, since tamoxifen is the post-treatment gold standard for us guys who are 90% ER+/HR+ HER2-.

I have a male friend who started on Femara nd went metastatic four years later, so the dilemma of changing from tamoxifen to an AI is not necessarily a sure bet.

That said, my friend has been going well on all the mets treatments for nearly four years now and his onc is holding back a few treatments should the current ones fail to work.


NED breast and prostate cancer. More on Male BC

Dx 03/14, IBC, Lgth. 2cm, Stge IIIB, Gde 2B, ER+/PR+, HER2- ; FEC x3, Taxol x3; Mx & 2/23 nodes; Rads x 33; now on tamoxofin.

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Feb 12, 2018 07:07PM solfeo wrote:

"Thus, such studies do not undermine the results of clinical trials that have established the therapeutic efficacy (benefit) of Tamoxifen or AIs in reducing distant recurrence, or the observed distant recurrence rates in patients receiving such treatments."

Correct in terms of the groups studied as a whole. If they are on the right track what it will do is identify the INDIVIDUALS who are more likely to recur within the existing larger statistical groups, where any person could fall on either end of the spectrum or anywhere in between. That doesn't mean my Oncotype DX score that gives me 9% chance of recurrence is wrong, statistically speaking, but it could mean I'm personally more likely to fall into the 9%. Statistics would eventually evolve as a result of the new information but that takes a long time and a lot of research.

I was going to add that AIs come with their own risk of developing resistance but that has now been said. I want to know exactly when tamoxifen has run its course so I can switch to an AI just in time to get the most life out of it too. Me and my pipe dreams!

Oncotype 13 Dx 7/31/2015, IDC, Right, 3cm, Stage IIA, Grade 1, 0/2 nodes, ER+/PR+, HER2- (FISH) Surgery 10/7/2015 Lymph node removal: Right, Sentinel; Mastectomy: Left, Right Hormonal Therapy 11/17/2015 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
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Feb 12, 2018 07:21PM - edited Feb 12, 2018 07:39PM by Lisey

Thanks BarredOwl, I was hoping you'd show up. The fact is Tamoxifen doesn't work for some women and men... I'm an ultra rapid processor, so the other side of Solfeo on that, but like her, I'd like to know if I have the ER36+ or if it's the normal ER66+. This will change my course of which hormonal I'll continue with. I don't think there's any way to test for this after the fact, or is it a simple blood test?

I will admit this study had me more upset than the one I just read saying that Asparagus leads to breast cancer. ugh. Everything leads to cancer.

Oncotype =20, ER 95%, PR 5%, ki67= 30%, Mammoprint = Low, Blueprint = Luminal A!!!! TEs= Iron Bra of Death - not worth all the complications for foobs that I'll never feel. Flat and fealess now. Dx 5/11/2016, IDC, Right, 1cm, Stage IA, Grade 2, 0/6 nodes, ER+/PR+, HER2- Surgery 6/1/2016 Lymph node removal: Sentinel Surgery 6/14/2016 Mastectomy: Left, Right; Reconstruction (left): Tissue expander placement; Reconstruction (right): Tissue expander placement Surgery 7/6/2016 Mastectomy: Left, Right Hormonal Therapy 7/14/2016 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
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Feb 13, 2018 06:48AM - edited Feb 13, 2018 06:49AM by voraciousreader

these investigations are a window into the future of genomics.....and how it will and already does influence screening, therapeutics and the mechanics of how cancer works.....


For those of you who are interested in these topics, but are intimidated by the studies and find them over your heads, try reading Eric Topol, M.D's The Creative Destruction of Medicine.


I wish to add, on a more sobering note, is that when The Genome Project announced back in 2000 that all of the genes were “identified"...there was great hope that disease would shortly be understood and eliminated. Back then, “junk DNA" was just that, junk! But, today, scientists appear more humbled. it seems the more they learn, the less they know and “junk DNA" has proven not to be junk after all. With all of that said, another provocative book, written by Columbia University Professor, Stuart Firestein, Ignorance, How it Drives Science, gives everyone hope. What Firestein discovered, is, when you put a group of scientists in a room and ask them what they are doing, they don't tell you what they know, they tell you what they are working on and hoping to learn and discover....


Studies like these show us the discovery process that will one day, which I hope will be soon, will lead to better screening, diagnostics, treatments and hopefully a cure...

Doctor told me regarding my prognosis that I WASN'T on the Titanic! Hmmm...Really?....Okay! 02/2010 Pure Mucinous Breast Cancer, Oncotype DX 15, Stage 1, Grade 1, 1.8 cm, 0/2 nodes, ER+ 90% /PR+ 70% HER2- (+1)
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Feb 13, 2018 09:14AM solfeo wrote:

There is a genetic disease that runs in my husband's family. The gene was discovered in 1993 and that came with promises of a cure within 5-10 years. When we found out my husband and son were at risk in 1998, we were told the scientists were 5-10 years away from a cure. Twenty years later we are probably still 5-10 years away. They have learned a lot in 25 years about what doesn't work and why, but not nearly enough about what does.

We weren't aware of the existence of the disease until after our son was born, and we chose to forgo having more children so as to not knowingly pass it on to another person. A lot of people took that promise of a cure around the corner to heart and had more children, counting on God and the scientists to save them. Some of those kids are dead now.

I'm not drawing any parallels to breast cancer research (I have high hopes), just agreeing with VR that "the more they learn, the less they know."
Oncotype 13 Dx 7/31/2015, IDC, Right, 3cm, Stage IIA, Grade 1, 0/2 nodes, ER+/PR+, HER2- (FISH) Surgery 10/7/2015 Lymph node removal: Right, Sentinel; Mastectomy: Left, Right Hormonal Therapy 11/17/2015 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
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Feb 13, 2018 10:50AM - edited Mar 8, 2018 12:08PM by BarredOwl

This Post was deleted by BarredOwl.
Stage IA IDC, 9/2013 BMX. Right: IDC (1.5 mm, grade 2) with DCIS (5+ cm), 0/4 nodes, pN0. Left: DCIS (5+ cm), 0/1 node, pN0(i+).

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