Wednesday, October 26, 2016

I Didn't Expect It To Feel Like This

My nephew had been struggling with a diseased foot for more than a year—it got infected and did not heal, likely a consequence of his type 1diabetes. He will have to have his leg amputated, a step that stunned the entire family. In discussing his concerns, my sister told me that he doesn't want his leg to just be cut off and thrown into the trash.

“That’s what they did with my breasts,” I said. “Cut them off and threw them away.”

Hearing this, the rest of the family was silent, sort of struck by my vehemence. I seldom give details about my breast cancer treatment—living through it once was enough—so this surprised us all. Me most of all.

I had no idea of the anger I had suppressed beneath a cheery I’ve-got-this exterior. And to have it come out so melodramatically and inappropriately—this was about Rod, not me—was embarrassing. But that’s the case with repressed anger. It doesn't go away; it just builds and eventually spews itself like a verbal volcano, scorching all in its path.

So we returned to Rod’s issue, and our hope that he could soon have surgery and that he would respond well. A month ago, doctors amputated his leg beneath the knee and he is healing well. He’ll be measured for a prosthesis in a few weeks.

Meanwhile, there’s me and my breasts in a surgical landfill somewhere.

My double mastectomy was the result of a second bout of triple-negative breast cancer. I had successfully recovered from my first round, in 2006, and was looking forward to celebrating ten years cancer-free. So I was more angered than anything when the beast roared its nasty head in the same breast in 2015, nine years almost to the day of my first diagnosis. The second cancer was small, but I easily opted for a double mastectomy, wishing I had done that the first time—just sliced the darn things off.

I didn't expect it to feel like this. Even after nine years of working with breast cancer patients, corresponding with hundreds, writing a book and scores of articles and starting a well-regarded cancer blog.

I look in the mirror and see a disfigured woman looking back. My surgery looks like hell, frankly. I have extra, uneven flaps on the bottoms and side of both former breasts. If I don't wear my prosthesis, these bumps show through my shirt, looking like tiny mole tunnels popping through my chest wall. A friend, who is a breast cancer surgeon and survivor, says this type of result frustrates doctors. The problem: docs operate on a woman while she is lying down and end up with a chest that is nice and even and flat and clean. But when the woman stands up, gravity takes over and packets of fat appear. These are not remainders of the breasts, but fat tissue that had surrounded them. Multiple docs have checked my surgical site and all is supposedly well—it’s healing as it is supposed to, and it falls within the fairly wide spectrum of normal. It just looks awful.

My surgical scars don't line up, probably because I'd already had a lumpectomy in my left breast. I see photos of women who have cool tattoos on their breasts and who proudly go flat, but they actually are flat, with a clear surgical line across their chests, not a jagged barbed-wire looking strip.

Of course, I could have plastic surgery to smooth things out, but I don't want more operations and more recuperation and more stuff added to my body. I do wish I’d had a plastic surgeon involved with surgery in the first place. But I now have much better understanding of why other women choose that route, especially younger women. I always got this intellectually, but now I get it emotionally.

I have several decent prostheses—a fancy gel-filled one that looks like a creature that washed up on a beach, a lighter foam set, and a cotton-filled number. The creature looks the best on, but the cotton one feels best. And I notice that, in photos, my body looks pretty trim and tight, with the kind of firm breasts you don't normally see on a 70-year-old. So whoop.

I feel great and continue to walk two miles a day and hike in the summer at our Colorado cabin. I’m writing another book and painting again and enjoying my family. My husband and I travel a lot and just enjoy one another in our down times.

So life, really, is good. And if Rod can move on after losing a leg that is essential to his mobility, I can be just fine losing breasts and having a chest that looks like a mistake.

Still, I retain the right to be grumpy.

Thursday, May 12, 2016

New Target for TNBC Found, Say UC Berkeley Researchers

University of California, Berkeley researchers have found a long-elusive Achilles’ heel within “triple-negative” breast tumors, a common type of breast cancer that is difficult to treat. The scientists then used a drug-like molecule to successfully target this vulnerability, killing cancer cells in the lab and shrinking tumors in mice.

“We were looking for targets that drive cancer metabolism in triple-negative breast cancer, and we found one that was very specific to this type of cancer,” said Daniel K. Nomura, an associate professor of chemistry and of nutritional sciences and toxicology at UC Berkeley and senior author for the study, which is published online ahead of print on May 12 in Cell Chemical Biology.

Triple-negative breast cancers account for about one in five breast cancers, and they are [Pat's edit: "they may be"] deadlier than other forms of breast cancer, in part because no drugs have been developed to specifically target these tumors
Triple-negative breast cancers do not rely on the hormones estrogen and progesterone for growth, nor on human epidermal growth factor receptor 2 (HER2). Because they do not depend on these three targets, they are not vulnerable to modern hormonal therapies or to the HER2-targeted drug Herceptin (trastuzumab). 

Instead, oncologists treat triple-negative breast cancer with older chemotherapies that target all dividing cells. If triple-negative breast cancer spreads beyond the breast to distant sites within the body, an event called metastasis, there are few treatment options.

Tumor cells develop abnormal metabolism, which they rely on to get the energy boost they need to fuel their rapid growth. In their new study, the research team used an innovative approach to search for active enzymes that triple-negative breast cancers use differently for metabolism in comparison to other cells and even other tumors. 

Inhibiting cancer metabolism
They discovered that cells from triple-negative breast cancer cells rely on vigorous activity by an enzyme called glutathione-S-transferase Pi1 (GSTP1). They showed that in cancer cells, GSTP1 regulates a type of metabolism called glycolysis, and that inhibition of GSTP1 impairs glycolytic metabolism in triple-negative cancer cells, starving them of energy, nutrients and signaling capability. Normal cells do not rely as much on this particular metabolic pathway to obtain usable chemical energy, but cells within many tumors heavily favor glycolysis.

Co-author Eranthie Weerapana, an associate professor of chemistry at Boston College, developed a molecule named LAS17 that tightly and irreversibly attaches to the target site on the GSTP1 molecule. By binding tightly to GSTP1, LAS17 inhibits activity of the enzyme. The researchers found that LAS17 was highly specific for GSTP1, and did not attach to other proteins in cells.

According to Nomura, LAS17 did not appear to have toxic side effects in mice, where it shrank tumors grown to an invasive stage from surgically transplanted, human, triple-negative breast cancer cells that had long been maintained in lab cultures.

The research team intends to continue studying LAS17, Nomura said, with the next step being to study tumor tissue resected from human triple-negative breast cancers and transplanted directly into mice. 

“Inhibiting GSTP1 impairs glycolytic metabolism,” Nomura said. “More broadly, this inhibition starves triple-negative breast cancer cells, preventing them from making the macromolecules they need, including the lipids they need to make membranes and the nucleic acids they need to make DNA. It also prevents these cells from making enough ATP, the molecule that is the basic energy fuel for cells.”

Beyond the metabolic role they first sought to track down, GSTP1 also appears to aid signaling within triple-negative breast cancer cells, helping to spur tumor growth, the researchers found.

Technique identifies Achilles' heels
Nomura said it was surprising that a single, unique target emerged from the research team’s search. 
The method used by the researchers, called “reactivity-based chemoproteomics,” can quickly lead to specific targetable sites — the Achilles’ heels — on proteins of interest, and eventually to drug development strategies, Nomura said.

The approach is to search for protein targets that are actively functioning within cells, instead of first using the well-trod path of surveying all genes to identify the specific genes that have taken the first step toward protein production. With that more conventional strategy, the switching on, or “expression,” of genes is evidenced by the easily quantified molecule called messenger RNA, made by the cell from a gene’s DNA template.
Nomura’s team instead first used chemical probes that can react with certain configurations of two of the amino acid building blocks of protein — cysteine and lysine — known to be involved in several kinds of important structural and functional transitions that active proteins can undergo.

 “A lot can happen after the first step in protein production, and we believe our method for identifying fully formed, active proteins is more useful for tracking down relevant differences in cellular physiology,” Nomura said.
The researchers analyzed and compared cells from five distinct triple-negative breast cancers that had been grown in cell cultures for generations, along with cells from four distinct breast cancers that were not triple negative. 

The scientists used a chemical identification technique known as mass spectrometry to narrow down the set of proteins that had active lysines and cysteines to just those that were metabolic enzymes. Only then did they use the more conventional approach of measuring gene expression in the different cancer cell types.

GSTP1 was the only metabolically active enzyme that was specifically expressed only in triple-negative breast cancer cells compared to other breast cancer cell types, the researchers found. Separate analysis of databases of human breast cancer by UC San Francisco co-authors confirmed that GSTP1 is overexpressed in patients with triple-negative breast cancers in comparison to patients with other breast cancers.

Thursday, March 31, 2016

Don't Eat At Night: One Way to Reduce Risk of Breast Cancer Recurrence

In patients with breast cancer, a short overnight fast of less than 13 hours was associated with a 36 percent higher risk of breast cancer recurrence, according to research published online  in the Journal of the American Medical Association Oncology.

Ideal, then, would be eating dinner no later than 7 p.m. and breakfast no earlier than 8 p.m. Not the standard American model, is it? This is the second study done on night-time fasting by researchers at the University of California, San Diego School of Medicine.  

Fasting fewer hours per night was associated with significantly less sleep and higher levels of glycated hemoglobin (HbA1c), which is a measure of average blood sugar levels over a period of months. Ellevated HbA1c and poor sleeping habits have been linked to an increased risk of breast cancer. These findings corroborate a paper published in April 2015, in which researchers demonstrated that shorter overnight fasts were associated with worse blood sugar control.

“Previous research has focused on what to eat for cancer prevention, but when we eat may also matter because it appears to affect metabolic health,” said Catherine Marinac, lead author and doctoral candidate at UC San Diego Moores Cancer Center. 

The study included 2,413 non-diabetic breast cancer survivors between the age of 27 and 70 studied between 1995 and 2007, with follow up for breast cancer recurrence and mortality. Participants were 86 percent non-Hispanic white and 55 percent were college educated.

“If future trials confirm that habitual prolonged nightly fasting improves metabolic health, this would be an important discovery in prevention that could reduce the risk of cancers, type 2 diabetes, and cardiovascular disease,” said Ruth Patterson, PhD, senior author and leader of the cancer prevention program at Moores Cancer Center.

Source: News release from University of California, San Diego School of Medicine.

Wednesday, March 16, 2016

Four Distinct Subtypes of TNBC

A study just published in Breast Cancer Research caught my eye because it provided additional perspective on why some TNBC tumors are so much more aggressive than others. Earlier research has shown that there are different forms of TNBC, but the classification in this particular study seemed a little clearer and more straightforward. Plus, the entire publication is easily accessible.

The gist of the recent research is that, as has been obvious for some time, basal-like TNBC tumors are the most likely to be aggressive. But there has been a lot of confusion just about everywhere on whether or not all TNBC tumors are basal-like. They are not, and this study shows how and why, and breaks TNBC into four different subtypes. It also might show why some TNBC tumors react to androgen therapy.

The report is pretty easy to track, so take some time to noodle it. The essential nugget, though, comes in the Results section of the Abstract:

All of the 165 TNBC tumors were classified into four distinct clusters, including an immunomodulatory subtype (IM), a luminal androgen receptor subtype (LAR), a mesenchymal-like subtype (MES) and a basal-like and immune suppressed (BLIS) subtype. The IM subtype had high expressions of immune cell signaling and cytokine signaling genes. The LAR subtype was characterized by androgen receptor signaling. The MES subtype was enriched with growth factor signaling pathways. The BLIS subtype was characterized by down-regulation of immune response genes, activation of cell cycle, and DNA repair. Patients in this subtype experienced worse recurrence-free survival than others (log rank test, P = 0.045). Subtype-specific lncRNAs were identified, and their possible biological functions were predicted using co-expression network analyses.

Read more about triple-negative breast cancer in my book, Surviving Triple-Negative Breast Cancer.  Want more content on this page? Make a donation. Just click the Donate button on the link on the right hand column of the blog.

Monday, February 15, 2016

Out of the Ashes

Out of the Ashes. Copyright Patricia Prijatel
I posted this on Cure magazine's gallery site and then realized I should actually share it here as well. I began painting this a couple of years ago, after a wildfire at our Colorado cabin. These are wallflowers, gorgeous, colorful little beauties that should make you feel better next time nobody asks you to dance. After the fire, friends told me we were in the midst of a resurrection, which was helpful as the whole ordeal was heartbreaking. So, when we started seeing these flowers growing through the ashes, it felt like a resurrection to me.

I started the painting before my latest diagnosis and finished it after. I was able to see the flowers  better then. Who knows why.

Also, I reduced this shot a lot just in case somebody should want to swipe them. I don't want my art to show up in an ad for some cheap erectile dysfunction drug.

Saturday, January 9, 2016

Life After Breast Cancer: Painting

The Road, by Patricia Prijatel                 copyright 2016
When I was in college and choosing careers, I was torn between being an artist and a writer. I chose not to be an artist because, to my teenage self, the only way an artist could make a decent living was by teaching and I didn't want to teach. Ironically, I ended up with a highly rewarding career as a writing teacher. Go figure.

Anyway, I am returning to my roots and doing things that I simply find enjoyable. This painting is of the road to our Colorado cabin.

Painting relaxes and exhilarates me, and I am proud of this one. The excellent photo of it comes from a talented photographer who is a former student from my teaching days.

So life goes on, in full color.

Wednesday, December 2, 2015

Six Months Post-Mastectomy: Seromas and Serenity

I watched the calendar a lot more carefully with my first cancer, counting the days until I reached the magic three-year mark for TNBC, then the five-year mark. This time, meh.

I’ve been doing fine, healing well after six months, with a few mild complications, as is to be expected with major surgery like a double mastectomy. But I am less attuned to this cancer than the last. I take fewer notes, do less research, just basically live my life with cancer in the rear-view mirror.

Enough, already.

I sort of think I know enough: eat well, exercise, breathe deeply, love, and laugh. That’s basically it, with or without cancer.

I am blessed with only occasional discomfort and no real pain. My chest is still pretty numb, but I am getting a bit more feeling. I have learned to gently massage the area formerly known as my breasts, which eases discomfort. If I get ahead of the game, it can prevent it. I use vitamin E oil on my scars.

Both give me a sense of pampering myself. Both feel good, period.

I wear my fancy breast prostheses sometimes, and sometimes not. No big deal either way.

But because I had already had a lumpectomy and sentinel node dissection plus radiation, I had to have a radical mastectomy on the affected breast the second time. This meant the possibility of more complications, especially seromas, or a build-up of fluids at the surgical site. That’s why we get the wonderful drains during surgery—to draw the liquid, or serum, from the wound. Sometimes, though, seromas return. Again and again, as they did in my case.

I was given the all-clear from my surgeon a month after surgery—no fluid build-up. All was good. We headed to our Colorado cabin where I apparently forgot about my surgery a tad too much. We’ve been trying to rebuild our land after a forest fire in 2013, and this year meant weed control. I tried to be reasonable and not pull the giant thistles , as I would otherwise have done. Instead I clipped their heads off. I also hiked a lot.

More damningly, possibly, I took several trips on the incredibly bumpy road to town—16 miles of a mix of dirt and gravel that has been worn by fire and logging trucks and torrential rains. Once I wore my Fitbit on the trip and it recorded that I climbed 52 sets of stairs, even though I was sitting in the car. Plus, I wore a seatbelt that dissected my chest, adding even more pressure. 

So, who knows exactly which of these activities caused it—maybe all, maybe none—but I ended back in the surgeon’s office with a 50 cc seroma. Then it was back to the land, with a somewhat modified routine. 

But we had no choice but to use that road. On one trip back from town, I was in huge pain by the time we got to the cabin. I pulled out the ice and Tylenol, but the next day I had a big red bruise in the crescent where my left breast had been. It got more colorful the next few days, and I could feel the fluid building up. It was nearly time to leave anyway, so we closed up the cabin and headed back to Iowa and the surgeon’s office.

This time he diagnosed it as an ecchymosis, basically a bruise, or a large hematoma. And he drained 165 cc of blood from it. Two weeks later, he drained 50 cc, but two weeks after that, nothing. I went another six weeks without a problem. Six weeks in which we drove more than 2,000 miles, exercised a lot, and acted normal, doing things like picking up my adorable grandsons (4 and 6) whenever I could—or whenever they would let me. No problems.

Then I got an interminable cold with a nasty cough that lasted more than a month. I hacked and wheezed and, soon, there was the red crescent on my chest again. Ugh. Did I cough so much I bruised my chest? Was it the drugs I was taking?  Both? Neither? Whatever, this time the doc drained 60 cc. I went back the next week and he said there was too little to drain.

So, a few steps forward, a few back. Quite the dance, but I have decided to stay home from this particular prom from now on.

I plan not to go back to the surgeon. He’s a great guy and I like him a lot, but I am tired of needles and other sharp things on my chest. I have returned to my acupuncturist, who is working on getting my lymphatic fluids moving. I am beefing up my mobility exercises and my pampering.  Should I get the bruise again, I will ice it and massage it more regularly and help it resolve itself.

I will be more proactive, less reactive. But I will always go on with my life.

Enough of the rocky road, figurative and real. Docs are not sure why seromas dog some women and not others. I certainly was at risk because of previous treatment, including radiation that weakened my skin. But, sometimes this just happens, and stewing about it gets you nowhere.

The fact is that seromas are not life-threatening. They are uncomfortable and annoying and, as a doctor friend told me, “frustrating for patient and doctor alike.” But I have never worried that they were a precursor of something more serious. There is no evidence of that.

I remember a moment when I was undergoing treatment for my first breast cancer, when I had this overwhelming feeling come over me, the certainty that I would be fine. And I was. Nine years with no recurrence. The second cancer certainly was a shock, but it was a tiny thing and was a second primary cancer, not a recurrence, so my prognosis has always been good.

The other day, I was engulfed in the same sort of feeling: that this was a turning point and things were going to settle after this. That, again, I would be fine. It just came over me unannounced, leaving me in spontaneous smiles. I am not sure of the source of this sense of wellness, goodness, and positive energy. Whatever it is, I will take it and run with it. Or, probably. walk.

Friday, August 28, 2015

Recovering in the mountains

We finally got to our Colorado cabin a couple of weeks ago. This is the meadow in front of the cabin. It's a great place to recover.  We had a forest fire here two years ago, so the land itself is recovering. We're quite the pair.

Monday, August 3, 2015

What Caused My Cancer?

When I speak to groups about breast cancer, I always make one important point: “You didn't cause your cancer.” I say it because I know women think it. What did I do? They beat themselves up with the what ifs and whys at a time when they need to be focused on building their physical, mental, and spiritual strength.

So, when I was diagnosed with a second primary cancer last month, one of my first thoughts was, “What did I do to cause this?”

Yeah, well. Do as I say and not as I do, I guess.

It’s inevitable that we go there, though, and it might even be somewhat worthwhile, if we can pull off an honest analysis without whipping up the blame. I did beat triple-negative breast cancer the first time nine years ago and plan to beat it again. But, to be truthful, the healthy lifestyle I adopted after my first diagnosis, which I credited with my ongoing good health, became a bit difficult to sustain. Was that a factor?

As you’ll see, just about everything could have caused this. If only I had been perfect.

1. Too much alcohol. The World Health Organization considers alcohol a carcinogen and says there’s no safe level of alcohol use, especially for those at risk of breast cancer. The more you drink, the greater your risk. Immediately after my first diagnosis, I had wine only on special occasions; at dinner I had organic black cherry juice in a wine glass, which was pretty delicious. Over the years I gradually started drinking more, adding martinis and an occasional shot of whiskey. At home I kept myself to one drink, but at dinners with friends, I had two or three glasses of wine. And this past winter I had some back problems and wine was the only sure-fire painkiller, so I would have only a glass, but it was a big one.

Research shows that alcohol is a bigger factor in estrogen-positive breast cancer than in TNBC, but it is still a factor. 

But here’s the thing about research on alcohol: It is done largely using surveys, so participants self-report their alcohol use. And human nature is such that we typically underestimate our bad behavior. So people who usually have three glasses of wine a day might report that they have one, and when they get cancer, that one measly glass is seen as dangerous, whereas the actual amount was three times that much.

2. Too few vegetables. And too many French fries and tacos. My original post-cancer diet nine years ago focused on at least five servings of vegetables and fruits, which has been shown to counter breast cancer, especially triple-negative. Eventually, I got a bit lazy and replaced some of the healthy stuff with unhealthy foods.

And I especially didn't eat enough dark, leafy greens, which are high in folate that can reduce breast cancer risk. Also, my stomach had been given me problems because of too many pills, so I even stopped taking the 600 micrograms supplement of folic acid that has been shown to reduce the effects of alcohol.

3. Change in exercise routine. This one is seriously weird and counter to all the research, but I think I finally figured it out. A year before my first diagnosis, I had begun to work out with a personal trainer and ultimately lost 50 pounds by jogging, increasing the length and speed of my walks, and eating fewer calories.  In the nine years since then, I had gained back 15 of those pounds, so this winter, I got a Fitbit and started increasing my exercise and reducing my calories. By the time I was diagnosed the second time, I had lost 10 of those pounds.

Why, with both of my diagnoses, did weight loss and increased exercise end up in cancer? I think it was because I had gained the weight in the first place and the cancer was already starting when I began to lose the pounds. So the weight loss probably helped me fight the cancer and kept it from returning, but it came too late to stop it from growing in the first place. Weight gain is directly associated with all forms of breast cancer, including TNBC.

My takeaway: Keep the exercise up and the pounds off. Don't get to the point at which increased exercise and reduced calories constitute a change. Make that the standard.

4. Radiation. The irony of breast cancer treatment is that it tends to put you at risk of second cancers. The National Cancer Institute warns that its Risk Assessment Tool for breast cancer is not appropriate for women who have had previous radiation treatment to the chest because this increases their chances of cancer. Not only did I have the standard 35-day radiation therapy, but I have had multiple chest x-rays since then for COPD. So my chest has had a lot of radiation, and radiation can cure as well as cause cancer.

5. Genetics. I have no family history of breast or ovarian cancer, although my Eastern European heritage puts me at increased risk of the BRCA1 or 2 genetic mutation. I really don't think this is genetic, though. I was 60 at the first diagnosis and 69 at the second, plus I have plenty of lifestyle issues that point to an increased risk.

Still, I think I live a lot healthier than most people I know—people who, by the way, don't get breast cancer twice—so there has to be some inherent tendency toward cancer in my DNA. Cancer, researchers say, is as unique as our DNA, so I have to factor in my own inherent whatever here. Plus, our DNA can be affected by factors in our broad environment—air, water, food, diet, stress—as well as by inherited traits. I was the fifth child, born when my mother was 40, so I often kid my siblings that I got the bad eggs. 
Also, I was born in December, and winter babies are more prone to sickness later in life, perhaps linked to winter illnesses, cold temperatures, and indoor pollutants while still in the womb.

Healthy lifestyle can combat DNA damage, which is good news, and reason to return to taking good care of my body.

So, no, I didn't cause this. Maybe I didn't do all I could to prevent it. I got sloppy and cocky and apparently I don't have the leeway I thought I did. I don't believe in guilt trips, but making this list has reminded me of all the good things I can, and should, do for myself.

That French fry or glass of wine is nowhere near as rewarding as a healthy body.