Clusters of P53 Protein Mutations Offer New Treatment Potentials for TNBC

The p53 protein in its natural state, sometimes called “the guardian of the genome,” is a front-line protector against cancer. But the mutant form appears in 50 percent or more of human cancers and in 80 percent of triple-negative breast cancers. It actively blocks cancer suppressors. Researchers at the University of Houston Rice University have discovered the same mutant protein can aggregate into clusters. These in turn nucleate the formation of amyloid fibrils, a prime suspect in cancers as well as neurological diseases like Alzheimer’s. The research was led by Peter Vekilov at the University of Houston (UH) and Anatoly Kolomeisky at Rice University. 

The condensation of p53 into clusters is driven by the destabilization of the protein’s DNA-binding pocket when a single arginine amino acid is replaced with glutamine, they reported. “It’s known that a mutation in this protein is a main source of cancer, but the mechanism is still unknown,” said Kolomeisky, a professor and chair of Rice’s Department of Chemistry and a professor of chemical and biomolecular engineering. “This knowledge gap has significantly constrained attempts to control aggregation and suggest novel cancer treatments,” said Vekilov, the John and Rebecca Moores Professor of Chemical and Biomolecular Engineering and Chemistry at UH. 

The mutant p53 clusters, which resemble those discovered by Vekilov in solutions of other proteins 15 years ago, and the amyloid fibrils they nucleate prompt the aggregation of proteins the body uses to suppress cancer. “This is similar to what happens in the brain in neurological disorders, though those are very different diseases,” Kolomeisky said. 

The p53 mechanism may be similar to those that form functional and pathological solids like tubules, filaments, sickle cell polymers, amyloids and crystals, Vekilov said. Researchers at UH combined 3D confocal images of breast cancer cells taken in the lab of chemical and biomolecular engineer Navin Varadarajan with light scattering and optical microscopy of solutions of the purified protein carried out in the Vekilov lab. Transmission electron microscopy micrographs of cluster and fibril formation contributed by Michael Sherman at the University of Texas Medical Branch at Galveston (UTMB) supported the main result of the study, as did molecular simulations by Kolomeisky’s group All confirmed the p53 mutant known as R248Q goes through a two-step process to form mesoscopic condensates. Understanding the mechanism could provide insight into treating various cancers that manipulate either p53 or its associated signaling pathways, Vekilov said. 

In normal cell conditions, the concentration of p53 is relatively low, so the probability of aggregation is low, he said. But when a mutated p53 is present, the probability increases. “Experiments show the size of these clusters is independent of the concentration of p53,” Kolomeisky said. “Mutated p53 will even take normal p53 into the aggregates. That’s one of the reasons for the phenomenon known as loss of function.” If even a small relative fraction of the mutant is present, it’s enough to kill or lower the ability of normal, wild-type p53 to fight cancer, according to the researchers. 

The Rice simulations showed normal p53 proteins are compact and easily bind to DNA. “But the mutants have a more open conformation that allows them to interact with other proteins and gives them a higher tendency to produce a condensate,” Kolomeisky said. “It’s possible that future anti-cancer drugs will target the mutants in a way that suppresses the formation of these aggregates and allows wild-type p53 to do its job.” 

Women Satisfied With "Going Flat" After Mastectomy

I have "gone flat," as have many women I know. That beguiling descriptor applies to breast cancer patients like me who do not have reconstruction after a mastectomy and therefore have pancake chests. After my bilateral mastectomy in 2015, I didn't want foreign material in my body. I miss my breasts, no doubt about it. In Western culture, breasts can define us as sexual beings; without mine, I feel a tad less desirable. Breasts equal beauty and I have the profile of a pencil. But I can remedy this with bras with prostheses that are comfortable and look natural, so why sign up for additional surgery and a continued need for medical surveillance?

Many other women choose differently, especially those who are younger; I understand and respect the importance of reconstruction for their own mental and physical well-being.

But my decision to “go flat” was right for me, and new research shows I am in good company.

The great majority of women who have decided against reconstruction are comfortable with their choice, according to a study published in the Annals of Surgical Oncology. READ THE STORY HERE.  

 

Looking for Research Participants in the UK on Building Resilience Online to Counter Psychological Effects of Breast Cancer

Readers in the UK: Here's your chance to participate in research through King's College London on   the psychological effects of breast cancer, and how to build resilience through online participation. From the news release:

Worrying (thinking about how things might go badly in the future), is normal from time to time, but for most people this passes fairly quickly. However, some people find that once they start worrying, it is very difficult to stop. Research studies have shown that people who are particularly resilient experience less worry and low mood. In the present study, we hope to increase resilience and decrease low mood and worry in people who have had breast cancer. We also want to find out how people find doing the intervention via the web-platform.

For more information, and to see if you are eligible, check out The Frame Project.

HDAC6 Effective in Metastatic TNBC

A news release from the George Washington University (GW) Cancer Center. 

Genetic modifier HDAC6 was found to control tumor growth and halt metastasis in triple-negative breast cancer in vivo, according to a new study published in the journal Cancer Research by investigators at the George Washington University (GW) Cancer Center.

Immunotherapy – the use of drugs to stimulate one’s own immune system to recognize and destroy cancer cells – has been successful in melanoma and other cancers. However, it has been less effective in breast cancer.

“There is an urgent medical need to find new ways to potentiate or increase the efficacy of immunotherapy in breast cancer, especially in aggressive and highly metastatic triple-negative breast cancer,” said Alejandro Villagra, PhD, member of the Cancer Biology Program at the GW Cancer Center and assistant professor of biochemistry and molecular medicine at the GW School of Medicine and Health Sciences. “Our research lays the groundwork for a clinical trial that could lead to new, life-saving treatment options for breast cancer patients that do not respond to conventional immunotherapies.”

Molecularly targeted agents, such as HDAC6 inhibitors, have been widely described in the research literature as cytotoxic – toxic to both cancerous and healthy cells. Villagra and his research team found new non-canonical regulatory properties of these epigenetic drugs, discovering that the inhibition of HDAC6 has a powerful and strong effect on the immune system unrelated to the previously cytotoxic properties attributed to HDAC inhibitors.

This research demonstrates for the first time that HDAC6 inhibitors can both improve response to immunotherapy and diminish the invasiveness of breast cancer, with minimal cytotoxic effects.

“We are excited about the work because, in addition to the potency of immunotherapy, this drug alone is capable of reducing metastasis,” said Villagra. “This could have implications beyond breast cancer.”

TNBC and CDK4/6 Inhibitors

Some good information here (OncLive) about TNBC and CDK4/6 Inhibitors, especially clarifying the different types of TNBC. Scroll toward the bottom of the article. 

An excerpt, from Ruth O’Regan, MD. chief of the Division of Hematology, Medical Oncology and Palliative Care within the Department of Medicine and associate director of Clinical Research at the University of Wisconsin Carbone Cancer Center:

However, when you look at TNBC, there is not just 1 type of breast cancer; there are 4 to 6 different types under that triple-negative umbrella. One of them is the luminal AR subtype, which looks like a luminal ER-positive subtype genomically, but is actually ER negative and AR positive. This led to some trials looking at single-agent antiandrogens to treat these AR TNBCs. Overall, both enzalutamide (Xtandi) and bicalutamide (Casodex) produced pretty modest activity. The question become, “How could we make these antiandrogen drugs more effective in these AR-positive TNBCs?” 

Need a Respite?

I had thought I was doing a decent job managing the stress of the pandemic, social unrest, my cancer advocacy and concerns, economic instability, the climate crisis, and everything that is 2020. I wasn't. 

Here's how nature helped and how it might help you too. 

Double rainbow on the ridge opposite my deck.

A deep sigh overwhelmed me as I sat down with a cup of tea on the deck of our mountain cabin—a shock down my neck, through my tense shoulders, to my arms, and into my clenched fingers. An unexpected, visceral response.

For a moment, I sat unmoving as my muscles contracted, then relaxed, and relaxed more. It felt almost violent. An emotional exorcism.

I often exhale a long, healthy sigh on this deck, a natural reaction to the miraculous calm and quiet before me. I look out at a meadow, across a tiny stream, over to a forested ridge. To my right looms the mountain in whose shadow we spend the summers.  

But this new reaction was far beyond that simple act of deep breathing. It felt more like an attack.

I had thought I was doing a decent job managing the stress of the pandemic, social unrest, my cancer advocacy and concerns, economic instability, the climate crisis, and everything that is 2020. That’s an incomplete list, and even reading it is stressful. I knew I was traumatized, but I was sure I was handling it just fine, what with being me and all.

Or not.

Our hummingbird feeder attracts gorgeous guys like this. You can put a feeder just about anywhere.

As I sat down in the mountain sun, I had unconsciously unleashed a batch of negative emotions that had skittered out of my body like little demons: fear, anxiety, anger, grief, stress, confusion, depression, disgust. More, I’m sure.

Most of us are facing post-traumatic stress disorder after the year that feels like a lifetime—and, in many ways, is. Those of us with cancer in our histories are especially susceptible to PTSD, even years after a diagnosis. How do we keep our lives, our communities, our country, and our planet afloat when we’re all hot zones of trauma? READ MORE

Burn Scars: A Memoir of the Land and Its Loss

Journalist Patricia Prijatel and her family built a tiny cabin in a remote Colorado mountain valley where they embraced the silent, the wild, and the beautiful—until June 2013 and the East Peak Fire. Their cabin survived, but their woodlands became a burn-scarred landscape of splintered trunks and blackened branches.

After the fire, the ruin of the land and its people grew: flash floods on eroded land, invasive weeds crowding out grass and seedlings, hurricane-level winds breaking healthy trees, dangerous orphaned animals, toxic air, and stress leading to life-threatening diseases, including a second diagnosis of triple-negative breast cancer.

Burn Scars: A Memoir of the Land and Its Loss follows Prijatel and her family through six years of living in a changed ecosystem. It’s the story of a love of the land, of hope challenging despair, of climate grief, and the birth of a climate warrior. With searing honesty, Prijatel chronicles an unprecedented transition for America's natural forests, the life they nurture, and the people witnessing their tragic loss. Her story serves as a love song, a warning, and a glimpse of the future we'll all navigate as climate change remakes the places we've loved. It's also a call to fight for a priceless treasure we can still preserve—if we act now.

"An honest and vulnerable meditation on the trauma of life in contemporary Colorado, put to the page with uncommon grace and insight. Prijatel is a compassionate guide in exploring that chaotic time. Most important, she offers hope for recovery and resilience."
Laura Pritchett, Author, Sky Bridge, winner of the WILLA Award

"An elegy and a wake-up call. Prijatel writes a deeply personal and wrenching story of loss that touches us all. Like fire, her memoir is a reckoning that urges us to examine our priorities and recognize our first allegiance is to the earth, our one true home." Karen Auvinen, Author, Rough Beauty: Forty Seasons of Mountain Living.

"A moving meditation on our connection to the land, and a potent wake up call to the devastating effects of climate change."Tanja Pajevic, Author, The Secret Life of Grief, winner of Nautilus Silver Award"

"An important story. Prijatel chronicles her personal journey of loss and climate grief that touches our collective experience. But it is also a story of healing, for as we face this crisis, we are challenged to discover a resilience within ourselves and in the generative power of nature." Leslie Davenport, Author, Emotional Resiliency in the Era of Climate Change.

Buy Burn Scars: A Memoir of the Land and Its Loss on Amazon

Get an autographed copy directly from the author.

Inflammation Caused by Radiation Can Fuel TNBC Cells: A New Road To TNBC-Specific Treatment?

From a News Release from ChristianaCare’s Cawley Center for Translational Cancer Research 

While radiation is successfully used to treat breast cancer by killing cancer cells, inflammation caused as a side-effect of radiation can have a contrary effect by promoting the survival of triple-negative breast cancer cells, according to research published online in the International Journal of Radiation Biology by Jennifer Sims-Mourtada, Ph.D., director of Translational Breast Cancer Research at ChristianaCare’s Helen F. Graham Cancer Center & Research Institute.

Accounting for 15-20% of all breast cancers, triple-negative breast cancer is faster growing than other types of breast cancers.

Dr. Sims-Mourtada’s latest study shows that inflammation caused by radiation can trigger stem-cell-like characteristics in non-stem TNBC cells.

“This is the good and the bad of radiation,” Dr. Sims-Mourtada said. “We know radiation induced inflammation can help the immune system to kill tumor cells — that’s good — but also it can protect cancer stem cells in some cases, and that’s bad.”

She added, “What’s exciting about these findings is we’re learning more and more that the environment the tumor is in – its microenvironment – is very important. Historically, research has focused on the genetic defects in the tumor cells. We’re now also looking at the larger microenvironment and its contribution to cancer.”

Triple-negative breast cancer cells don’t have estrogen or progesterone receptors and also don’t make too much of the protein called HER2—cells test “negative” on all 3 tests. These cancers tend to be more common in women under age 40, who are African-American, Latina or who have a BRCA1 mutation. But older women, caucasian, those with no family history of breast cancer, and no genetic mutations can be affected.

“My work focuses on cancer stem cells and their origination,” Dr. Sims-Mourtada said. “They exist in many cancers, but they’re particularly elusive in triple-negative breast cancer. Their abnormal growth capacity and survival mechanisms make them resistant to radiation and chemotherapy and help drive tumor growth.”

She and her team applied radiation to triple-negative breast cancer stem cells and to non-stem cells. In both cases, they found radiation induced an inflammatory response that activated the Il-6/Stat3 pathway, which plays a significant role in the growth and survival of cancer stem cells in triple-negative breast cancers. They also found that inhibiting STAT3 blocks the creation of cancer stem cells. As yet unclear is the role IL-6/STAT3 plays in transforming a non-stem cell to a stem-cell.
For women living in Delaware, Dr. Sims-Mourtada’s research is especially urgent: The rates of triple-negative breast cancer in the state are the highest nationwide.

Dr. Sims-Mourtadato recently received a grant to continue investigating the role of cells immediately around a tumor in spurring the growth of triple-negative breast cancer and a possible TNBC-specific therapy.“Our next step is to understand the inflammatory response and how we might inhibit it to keep new cancer stem cells from developing,” she said.

Her research team previously identified an anti-inflammatory drug, currently used to treat rheumatoid arthritis, that has the potential to target and inhibit the growth of cancer stem cells and triple-negative breast cancer tumors. That research could set the stage for clinical investigation of the drug, alone or in combination with chemotherapy, to improve outcomes for patients with triple-negative breast cancer.

Researchers Starve Triple Negative Breast Cancer With Drug in Clinical Trials

From A News Release from Science Daily

Brazilian researchers have developed a strategy that slows the growth of triple negative breast cancer cells by cutting them off from two major food sources.

Triple-negative breast cancer, or TNBC, makes up approximately 15% to 20% of all breast cancers and is most common in African American women. These tumors lack estrogen and progesterone receptors and HER2 protein which are present in other breast cancers and permit certain targeted therapies. And because every TNBC tumor has a different genetic makeup, finding new markers that could guide treatment has been a difficult task.

"There is intense interest in finding new medications that can treat this kind of breast cancer," said Sandra Martha Gomes Dias, a cancer researcher at the Brazilian Biosciences National Laboratory in Campinas, Brazil. "TNBC is considered to be more aggressive and have a poorer prognosis than other types of breast cancer, mainly because there are fewer targeted medicines that treat TNBC."

In a new study in the Journal of Biological Chemistry, Dias and colleagues demonstrate that in addition to glutamine, a well-known cancer food source, TNBC cells can use fatty acids to grow and survive. When inhibitors that block both glutamine and fatty acid metabolism were used in concert, TNBC growth and migration slowed, Dias said.

To maintain their ability to grow at a breakneck pace, cancer cells consume nutrients at an increased rate. Glutamine, which is the most abundant amino acid in plasma, is one of them. Some types of cancer become heavily reliant on this versatile molecule as it offers energy, carbon, nitrogen, and antioxidant properties, all of which support tumor growth and survival, Dias said.

The drug Telaglenastat, also known as CB-839, prevents the processing of glutamine and is currently in clinical trials to treat TNBC and other tumor types. CB-839 works by deactivating the enzyme glutaminase, preventing cancer cells from breaking down and reaping the benefits of glutamine. However, recent research has shown that some TNBC cells can resist the drug treatment.

To see if alterations in gene expression could explain how these cells survive, the authors of the study exposed TNBC cells to CB-839, defined those that were resistant and those that were sensitive to the drug, and sequenced their RNA, Dias said.

In the resistant cells, molecular pathways related to the processing of lipids were highly altered, Dias said. In particular, levels of the enzymes CPT1 and CPT2, which are critical for fatty acid metabolism, were increased.

"CPT1 and 2 act as gateways for the entrance of fatty acids into mitochondria, where they will be used as fuel for energy production," Dias said. "Our hypothesis was that closing this gateway by inhibiting CPT1 in combination with glutaminase inhibition would decrease growth and migration of CB-839-resistant TNBC cells."

The double inhibition proved significant as it slowed proliferation and migration in resistant TNBC cells more than individual inhibition of either CPT1 or glutaminase. These results provide new genetic markers that could better guide drug choice in patients with TNBC, Dias said.

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Metabolic Syndrome and TNBC

Improving metabolic factors may help improve survival in postmenopausal women with triple-negative breast cancer, according to research presented at the 2019 San Antonio Breast Cancer Symposium. These factors, which include weight gain, reduced activity and insulin resistance, can be an issue for women diagnosed with TNBC and may have serious repercussions for health overall. 

Researchers compared these factors, also called metabolic syndrome, with survival rates in women diagnosed with TNBC who participated in the Women’s Health Initiative (WHI), enrolled from 1993 to 1998. 

The average time from enrollment to TNBC diagnosis was 8.6 years; women with the most metabolic components had a significantly shorter time (7 years) to diagnosis than those without any metabolic syndrome components (9.8 years). Women with TNBC and 3 to 4 metabolic components had 10-year all-cause survival rates 35% lower than TNBC survivors with no metabolic syndrome components.

• 29% of the women (178 patients) had no metabolic syndrome components.

• 53% had 1 to 2 components (323 patients).

• 7% had 3 to 4 components (43 patients). 

• Those with the most metabolic syndrome components were often black. 

• Patients with income under $50,000 a year were more likely to have a greater number of metabolic components. 

The conclusion: Greater attention should be given to issues such as weight gain, physical activity, and insulin levels. 

This site is entirely volunteer. Please consider a small (or large would be fine) donation. You can donate here.

Watch the Scary TNBC Language!!!

I just got a news release from the University of Connecticut about gene splicing and how that can lead to triple-negative breast cancer. It's the beginning of what could be promising research for a targeted therapy for TNBC.

BUT, in the middle of the release is this utterly outrageous sentence:

Triple negatives are the worst breast cancers: they have the highest rates of metastasis, worst prognosis, and no targeted treatments. 

My edit

Triple negative breast cancer can be more aggressive than hormone-positive cancer, but it responds well to chemotherapy. Metastatic TNBC so far has no targeted treatment.

Later in the release, they call TNBC "this most dreaded form of breast cancer."

I am livid! This is irresponsible and wrong. I was diagnosed in June 2006, 13.5 years ago. I had a second cancer in June 2015, 4.5 years ago. I'm doing fine. I didn't like the experience, but I survived, as do most women with TNBC. 

Aurghhhhh. 

This site is entirely volunteer. Please consider supporting this work through your donation.

Acupressure can reduce effects of breast cancer treatment.

Acupressure improved some of the most common side effects of breast cancer treatment, including chronic pain, anxiety, depression, and poor sleep, according to a study published in JNCI Cancer Spectrum.

READ MORE HERE.

Who Is Most Likely to Get Triple-Negative Breast Cancer?

In an extensive survey of more than a million cases of breast cancer diagnosed between 2010 and 2014, researchers have reaffirmed that triple-negative breast cancer (TNBC) is most likely to affect black and Hispanic women and women younger than 40. This is nothing new, but the large number of the group studied gives significant support to previous research. According to the study, published in the journal Cancer, 8.4 percent of all cases were triple-negative, a smaller number than in previous research that showed that 10-20 percent of all breast cancer cases were TNBC. READ MORE

Fiction Helps Me Escape to the Warmth

Thanks, Louise Penny, for reminding us of what's warm, 

welcoming and a bit silly.

It’s usually winter in Three Pines, a village hidden in a forested Canadian valley somewhere between Quebec City and Montreal. The enchanting hamlet doesn't actually exist, although it should, and many of us prefer to think it does. Author Louise Penny created this tiny burg out of her imagination and bits and pieces of the Eastern Townshipsof Quebec, Canada, just north of the Vermont border.

Having read all of Penny’s books about this quirky but welcoming place, I understand why Penny seldom sets her stories in spring or summer.  The frigid Canadian weather allows the residents to gather around fires in the bistro or in the home of one friend or another, to share bowls of steaming soup and fresh bread, to demonstrate physical and emotional warmth and, of course, to help the wise and indestructible Chief Inspector Armand Gamache work out his latest mystery.

The warmth is more potent when pitted against intense cold. The light is stronger when compared with the dark. And it’s easy to overlook that Penny writes a good deal about evil and violence because those become just dark shadows in an otherwise hospitable world. The mystery part of her novels is incidental. We're there for the people.

The hub of Three Pines  is the village green around which the bistro, bookstore, bakery and B&B are all grouped and where the three trees grow, within walking distance of the homes of the oddball inhabitants: Ruth, the renowned poet who nurtures nothing but her foul-mouthed duck; Myrna, a retired psychologist who owns the cozy bookstore; Clara, the artist whose work is far more complicated than it appears; Gabri and Olivier who run the bistro and B&B, gay men who have found a home in this tolerant town; and Armand and his wife Reine-Marie, who adore one another 35-plus years into marriage.

The group meets often for meals and drinks and problem-solving, often related to crimes, often related to their personal lives, always related to food. Book by book, these characters become closer to one another, grow more fully themselves, and build a community too delightful to be real, although readers can dream.

Travel bureaus in the Eastern Townships know a winner when they see it, and they provide maps, web sites, and formal tours of favorite places in the Gamache novels. The bistro where the gang meets? It could be one of several in Knowlton. The church where the body of the mysterious debt collector was found? It’s just outside Sutton. The monastery where Gamache investigated the death of the music director? It’s the gorgeous Abbaye De St-Benoit-Du-Lac, or St. Benedicts on Lake Memphremagog.  Try to say that with a mouth full of brioche. READ MORE.

Music helps soothe breast cancer pain

Breast cancer treatment can be miserable—doctors cut you up, fill you with toxins, and radiate you. It’s physically and mentally grueling, and it can exhaust patients for months, even years, after treatment ends. Surgery and radiation can leave permanent pain.

Listening to music at home can help. READ MORE.

Five Truths About Triple-Negative Breast Cancer That Can Give You Hope

It’s maddening that come patients are being denied the hope they need when diagnosed with triple-negative breast cancer (TNBC). Mind you, TNBC is nothing to mess with, but my mantra through my 13 years living through and writing about the disease is, “Most women with TNBC survive and go on to live full lives.” I’ve heard that fact spoken by numerous top researchers through the years. And we have the evidence to support that statement.

So let’s talk about a few facts that may help settle some fears.

1. The disease-free survival rate five years after diagnosis for TNBC is 77 percent. Yes, that is not as good as hormone-positive cancer (93 percent), but it means the odds are still seriously in your favor. And in some studies, the survival rate for TNBC was as high as 85 percent. With continued research, improved tools for early diagnosis, and new treatment options, survival rates for women being treated now are likely to be much higher than that.  

2. If TNBC is going to recur, it will usually do so within the first three years after diagnosis.  

3. After five years, your chances of recurrence are minimal. Ninety-seven percent—as in almost all—of those who survived five years recurrence-free remained so after ten years and 95 percent were recurrence-free after 15 years.  

4. Survival rates are measured from time of diagnosis, so you may be closer than you think to the magic five years.

5. If you have a second cancer, especially several years after your original diagnosis, it might be a second primary, and not a recurrence.  I repeat: Not a recurrence. With a second primary, you’re just starting from the beginning, with a new cancer. Not ideal, but a with significantly better prognosis than a recurrence. Some types of cancer treatment, such as chemo and radiation, can make you more susceptible to a second primary. I have survived the first diagnosis for 13 years and the second for four years, with no signs of disease.

•This site is entirely volunteer. Please consider supporting this work through your donation.

For More Research:

Surviving Triple-Negative Breast Cancer: Hope, Treatment and Recovery, by Patricia Prijatel. (That's me.)

Long-term survival outcomes of triple-receptor negative breast cancer survivors who are disease free at 5 years and relationship with low hormone receptor positivity, British Journal of Cancer. January 2018

Predictive factors and patterns of recurrence in patients with triple negative breast cancer. Annals of Surgical Oncology, February 2014

Constructing a Clinicopathologic Prognostic Model for Triple-Negative Breast Cancer, Physician Education Resource, 2017

Triple-Negative Breast Cancer: Clinical Features and Patterns of Recurrence, Dent et al. Clinical Cancer Research, August 2007

Understanding Statistics Used to Guide Prognosis and Evaluate Treatment, American Society of Clinical Oncology.   

Assessing the prognostic factors, survival, and recurrence incidence of triple negative breast cancer patients, a single center study in Iran. PLOS1, January 2019

Study Shows Mammography Saves Lives

Hundreds of thousands of women's lives have been saved by mammography and improvements in breast cancer treatment since 1989, according to a study published in CANCER, a peer-reviewed journal of the American Cancer Society.

According to the report,,female breast cancer mortality rates in the United States increased by 0.4% per year from 1975 to 1990. Since 1990, those rates have fallen between 1.8% and 3.4% per year, a decrease that is attributed to increased mammography screening and the improved treatment.

Estimates range from more than 305,000 to more than 483,000 women whose lives were saved between 1990 and 2015, depending on different background mortality assumptions.Researchers estimated that in 2018 alone, an estimated 27,083 to 45,726 breast cancer deaths were averted. 

Researchers analyzed breast cancer mortality data and female population data for U.S. women aged 40 to 84 years over the past three decades.

“Recent reviews of mammography screening have focused media attention on some of the risks of mammography screening, such as call-backs for additional imaging and breast biopsies, downplaying the most important aspect of screening—that finding and treating breast cancer early saves women's lives. Our study provides evidence of just how effective the combination of early detection and modern breast cancer treatment have been in averting breast cancer deaths,” said R. Edward Hendrick, PhD, of the University of Colorado School of Medicine,

Only about half of U.S. women over 40 years of age currently receive regular screening mammography, he said. “The best possible long-term effect of our findings would be to help women recognize that early detection and modern, personalized breast cancer treatment saves lives and to encourage more women to get screened annually starting at age 40.”

[PAT'S NOTE:] Both my cancers were caught early on mammograms, so I'm onboard with this one.

Weight Gain Associated with TNBC Risk

In a study of postmenopausal women, participants who lost weight had a lower risk of developing triple-negative breast cancer than those who maintained or gained weight. The research was published online in CANCER, a journal of the American Cancer Society.

The findings suggest that weight loss may help lower postmenopausal women’s breast cancer risk. [NOTE: I was postmenopausal and I lost weight right before I was diagnosed with TNBC—both times.]

Although obesity has been strongly related to breast cancer risk, studies examining whether weight loss might reduce postmenopausal women’s risk have provided mixed results. To examine the issue, Rowan Chlebowski, MD, PhD, of the City of Hope National Medical Center in Duarte, California, and his colleagues analyzed information on 61,335 women participating in the World Health Initiative Observational Study who had no prior breast cancer and had normal mammogram results. The women’s body weight, height, and body mass index were assessed at the start of the study and again 3 years later. 

During an average follow-up of 11.4 years, there were 3,061 new cases of invasive breast cancer diagnosed. Women with weight loss at 5 percent or more had a 12 percent lower breast cancer risk compared with stable weight women, with no interaction by body mass index. Weight gain of 5 percent or more was associated with a 54 percent higher incidence of triple negative breast cancer.

“Our study indicates that moderate, relatively short-term weight reduction was associated with a statistically significant reduction in breast cancer risk for postmenopausal women,” said Dr. Chlebowski. “These are observational results, but they are also supported by randomized clinical trial evidence from the Women's Health Initiative Dietary Modification trial where, in a randomized clinical trial setting, adopting a low-fat dietary pattern that was associated with a similar magnitude of weight loss resulted in a significant improvement in breast cancer overall survival. These findings, taken together, provide strong correlative evidence that a modest weight loss program can impact breast cancer.”
 

Nanoparticles Improve TNBC treatment

The chemotherapy drug doxorubicin encapsulated in nanoparticles an be especially effective in treating triple-negative breast cancer, according to a study published in Precision Nanomedicine.   

Researchers found that increased cell kill in triple-negative breast cancer cells was associated with the smallest size of nanoparticles and the slowest release of doxorubicin.

"Nanomedicine is a very exciting avenue in modern drug development," said Adam Friedman, MD, director of the Supportive Oncodermatology Clinic at GW Cancer Center, professor of dermatology at the George Washington School of Medicine and Health Sciences, and senior author of the study. "Nanotechnology offers many benefits, including the ability to purposefully customize your drug or diagnostic at the atomic scale, enhancing its ability to interact with its biological target and improve outcomes and potentially safety."

Friedman acknowledges that this study is an initial step, but it "provides clues for new potential strategies utilizing and manipulating nanotechnology to overcome cancer cell drug resistance. We have our work cut out for us, but this study shows that we are moving in the right direction."

Eating Bacon Might Increase Your Breast Cancer Risk

A new study in the International Journal of Cancer reviewed previous research on the link between meat consumption and breast cancer risk and concluded that processed meat increases your breast cancer risk significantly. This includes bacon, ham,  sausage, hot dogs, salami, and beef jerky.

Researchers found that eating processed meat was associated with a 9% higher breast cancer risk. Interestingly, they found no significant association between red (unprocessed) meat intake and risk of breast cancer. Risk was increased in both ER-negative and ER-positive cancers. Of the 15 studies, two found a greater link between a diet of processed meat and ER-negative cancers.  

"Cutting down processed meat seems beneficial for the prevention of breast cancer,” said lead author Dr. Maryam Farvid, of the Harvard T.H. Chan School of Public Health.