Breast Cancer Relapse: New Clues

Today, I wanted to chat less about wellness, and turn to breast cancer; more specifically, to a generally favorable type driven by estrogen. Why might some patients with this entity relapse, while most do not?

A large genomic analysis has linked certain DNA mutations to a high risk of relapse in estrogen receptor positive breast cancer, while other mutations were associated with better outcomes, according to researchers from Washington University School of Medicine in St. Louis, the Baylor College of Medicine and the University of British Columbia. The study appears Sept. 4 in the journal Nature Communications.

Why might this finding be important? The knowledge could help predict which patients are most likely to have their cancer return and spread, and could help guide treatment decisions. It also opens the door to developing more aggressive treatments for patients with the newly identified high-risk mutations.

The researchers analyzed tumor samples from more than 2,500 patients with estrogen receptor positive breast cancer, one of the most common forms of the disease. These cancer cells have receptors that bind to the hormone estrogen in the nucleus of the cell and drive tumor growth.

Management options

Estrogen receptor positive (ER +) breast cancer patients have a number of treatment options that block the estrogen receptor to stop tumor growth. Such hormonal therapies are effective and less toxic than traditional chemotherapy and radiation. But some tumors develop resistance to these treatments, mutating in ways that fuel growth independent of the presence of estrogen. These types of mutations are of great interest because they are responsible for the majority of deaths due to breast cancer.

Why recurrence?

The new study confirmed past work showing that relatively common mutations in genes called MAP3K1 and TP53 had opposite effects on tumor aggressiveness. Patients with MAP3K1 mutations did well, while those with TP53 mutations were likely to have a recurrence. The study also identified three genes — DDR1, PIK3R1 and NF1 — with relatively uncommon mutations that were associated with cancer recurrence and spreading.

Going forward, these genes will likely be included in gene panel tests, particularly when clinical trials are developed that target these mutations. Scientists now have enough healthy genomes sequenced to be able to compare, on a broad population level, normal genomes to cancer genomes and use big data bioinformatics methods to pull out the mutations likely to be driving cancer, even in old samples that can’t be directly compared with healthy DNA from the same patient. This study illustrates that continuing breast cancer gene sequencing may yield information that may help with establishing prognosis, and give us new targets for treatment. I’m Dr. Michael Hunter.

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I received an undergraduate degree from Harvard, a medical degree from Yale, and completed a residency in radiation oncology at the University of Pennsylvania. I have been blessed to be named a “top doctor” in Seattle Magazine, US News & World Report, Seattle Metropolitan Magazine, 425 Magazine, and WA magazine. On multiple occasions, readers of the Kirkland Advertiser have voted me the top doctor (in any field) in the region. I help individuals with cancer at Evergreen Hospital, just outside Seattle. And now the small print: Any information provided herein is not to serve as a individualized advice, and I encourage you to check in with a valued health care provider.

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https://www.sciencedaily.com/releases/2018/09/180904114708.htm

Stage IV Breast Cancer: Some Good News

I recently had a patient who presented with Stage IV (cancer associated with spread to distant sites such as the lungs, liver, bone, or brain). Given her cancer is associated with HER2 over-expression, I wondered what her long-term odds of survival would be. A retrospective study provides some answers:

For those who are found to have distant spread of cancer at initial diagnosis, patients with HER2-positive breast cancer treated with HER2-directed therapy had a median overall survival of 5.5 years. And for the 13 percent of patients who achieved a no evidence of disease status, the 5 year progression-free survival odds were an amazing 100 percent! Amazingly, the results held at the ten year mark.

For the unfortunate group of patients who did not achieve a no evidence of disease status, the 5 year progression free survival rate was 12 percent, and the overall survival rate 45 percent. By ten years, these numbers dropped to 0% for progression free survival, and only 4 percent for overall survival.

Now, some details… The results were the product of an analysis of 483 patients diagnosed between 1998 and 2015 at M.D. Anderson Cancer Center and Yale. All patients received Herceptin (trastazumab), and 20 percent also received pertuzumab as first-line therapy.

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Thank you.

_________________________

I received an undergraduate degree from Harvard, a medical degree from Yale, and completed a residency in radiation oncology at the University of Pennsylvania. I have been blessed to be named a “top doctor” in Seattle Magazine, US News & World Report, Seattle Metropolitan Magazine, 425 Magazine, and WA magazine. On multiple occasions, readers of the Kirkland Advertiser have voted me the top doctor (in any field) in the region. I help individuals with cancer at Evergreen Hospital, just outside Seattle. And now the small print: Any information provided herein is not to serve as a individualized advice, and I encourage you to check in with a valued health care provider.

Oncologist 2018 Aug 23;[EPub Ahead of Print], Y Wong, AS Raghavendra, C Hatzis, JP Irizarry, T Vega, N Horowitz, CH Barcenas, M Chavez-MacGregor, V Valero, D Tripathy, L Pusztai, RK Murthy

Breast Cancer: Are You Over 70?

The 21-gene recurrence score (RS), known as OncoType Dx is a fabulous way of interrogating the breast cancer genome to ask some simple, but critical questions: Are you a secretly aggressive cancer? Would you respond to chemotherapy or not? While the test can be invaluable for select patients with hormone receptor positive breast cancer, the OncoType has not been validated in an older cohort with estrogen receptor-positive breast cancer.

The study

Now comes a study of the US Surveillance, Epidemiology, and End Results (SEER) database with available OncoType Recurrence Scores. Researchers evaluated women with estrogen receptor-positive breast cancer ages 18 to 69 and those 70 years of age and older from 2004 to 2014. They presented their results in the Journal of Geriatric Oncology earlier this month.

The results

Among patients with a high-risk recurrence score, chemotherapy was associated with a decreased risk of death in the younger group, but not the older group.

My take

Older women are less likely to have OncoType testing (8 percent versus 18 percent), but when tested, older patients have a similar distribution of Recurrence Scores as do the younger women. However, while being in the high-risk group was prognostic irrespective of age, chemotherapy was not associated with an improved survival for the older population. I’m Dr. Michael Hunter.

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I received an undergraduate degree from Harvard, a medical degree from Yale, and completed a residency in radiation oncology at the University of Pennsylvania. I have been blessed to be named a “top doctor” in Seattle Magazine, US News & World Report, Seattle Metropolitan Magazine, 425 Magazine, and WA magazine. On multiple occasions, readers of the Kirkland Advertiser have voted me the top doctor (in any field) in the region. I help individuals with cancer at Evergreen Hospital, just outside Seattle. And now the small print: Any information provided herein is not to serve as a individualized advice, and I encourage you to check in with a valued health care provider.

Breast Cancer: Can THIS Lower Your Risk?

I hope you are having a great day. Here in Seattle, we are looking at sunny and a temperature of 71F (22C). While we have largely focused on wellness (including musings on the benefits of meditation and of sex), today I want to talk a bit about a recent study from researchers from the University of California, San Diego (USA). I am often asked about vitamins and cancer risk reduction, and to be frank, most studies have not shown a benefit to taking vitamins, at least with respect to cancer risk reduction; here, I am a big advocate of getting our cancer-fighting nutrients through diet.

A lower risk of breast cancer is found among older women who have greater levels of vitamin D, according to a study from the University of California, San Diego.

While the study doesn’t prove cause and effect, it’s the latest among many that find those with higher levels of vitamin D have lower risks of various diseases. It was recently published in the journal PLOS ONE, and can be found at j.mp/vitdbcancer.

Women with the highest levels of vitamin D in the blood had 20 percent of breast cancer risk as those with the lowest levels.

Researchers used data from two randomized clinical trials with a total of 3,325 participants, and another study with 1,713 participants. All participants were women 55 and older. Their blood was examined between 2002 and 2017 for the main form of vitamin D in the blood. 25(OH)D. This was correlated with any diagnosis of breast cancer.

Over the course of the studies, 77 new cases of breast cancer were diagnosed. Participants with blood levels above 60 nanograms per milliliter had just 20 percent of the risk, compared to those those with less than 20 ng/ml.

But…

The official recommended level of vitamin D is set at 20 ng/ml by the National Academy of Medicine, an advisory body to the president and Congress on health issues. The issue remains hotly debated, in part because the evidence at this point is mostly associational, not causal.

“Increasing vitamin D blood levels substantially above 20 ng/ml appears to be important for the prevention of breast cancer,” co-author Sharon McDonnell, an epidemiologist and biostatistician for GrassrootsHealth, said in a statement.

Garland said the study was limited to postmenopausal breast cancer, and mainly included white women. So more research is needed on whether high vitamin D levels might protect against premenopausal breast cancer, including other ethnic groups,

To reach the recommended blood level of vitamin D, Garland said daily supplements of 4,000 to 6,000 international units are required. This can also be achieved at low latitudes, such as in Southern California, by wearing minimal clothing in the sun for 10 to 15 minutes per day.

The National Academy of Medicine recommends 400 IU of vitamin D3 daily for infants; 600 IU for those 1 to 70 years, and 800 IU for those over 70.

Other studies have examined the correlation of various diseases with exposure to sunshine, which the body uses to produce vitamin D. The studies found lower incidences of various diseases with lower latitudes, and higher levels at higher levels. When charted, this association produces a curve that’s called the “vitamin D smile.”

Not So Fast…

Now, should you run out and start taking a ton of vitamin D? We have no evidence that doing so will reduce your risk of breast cancer. Everything in moderation. For me, that means a sojourn to Hawaii in February, as we can make 5,000 IU in 10 to 15 minutes of “reasonable” sun: That means 8 to 10 in the morning, after 4 in the afternoon. No sunburns, please! I’m Dr. Michael Hunter, and I thank you for letting me ramble a bit on this sunny and glorious Seattle Tuesday!

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I received an undergraduate degree from Harvard, a medical degree from Yale, and completed a residency in radiation oncology at the University of Pennsylvania. I have been blessed to be named a “top doctor” in Seattle Magazine, US News & World Report, Seattle Metropolitan Magazine, 425 Magazine, and WA magazine. On multiple occasions, readers of the Kirkland Advertiser have voted me the top doctor (in any field) in the region. I help individuals with cancer at Evergreen Hospital, outside Seattle. Any information provided herein is not to serve as a substitute for the good judgment of your valued health care provider. Thank you.

References

Primary source

Vitamin D and Breast Cancer

Breast Cancer: Omega-3 Fatty Acids for Side Effects

While I have spent the last several days blogging about mindfulness (and meditation in particular), today I want to talk about a challenging problem for many women with breast cancer. The vast majority of breast cancer feeds off the “female” hormone estrogen; that is, they tend to be hormone receptor positive (estrogen- and/or progesterone receptor positive).

For women who have completed menopause, we often offer pills that target the estrogen creation pathway, using drugs known as aromatase inhibitors. Unfortunately, about half of patients will experience associated pain in bones, joints, or muscles. This prompts many to simply quit this prognosis-improving drug. Researchers recently used a retrospective analysis of the use of omega-3 fatty acids to see whether it could reduce pain. Here’s what they found:

Omega-3 fatty acids significantly reduced pain among very overweight women who take aromatase inhibitors (AIs) for breast cancer.

The findings are potentially good news because, among postmenopausal women with hormone receptor–positive breast cancer, aromatase inhibitors can prolong survival but are often discontinued because of often severe joint pain.

The new results come from the Southwest Oncology Group (SWOG) Study S0927, a 24-week randomized controlled trial of omega-3 fatty acids versus placebo (inert pill) for aromatase inhibitor-related bone pain. The original results were disappointing, showing no difference in pain reduction between the treatment and placebo groups.

However, researchers suspected that heavier women were benefitting from the therapy. So, in the new study, they divided the women into two groups by weight. Among the 249 participants, 139 had a body mass (BMI) less than 30 (56%) and 110 had a BMI of 30 or higher (44%).

Joint-specific symptoms were also significantly lower at 24 weeks (compared to baseline) in the omega-3 fatty acid group  — but only in women with a BMI of 30 or more, said Shen.

The study results must be confirmed in a prospective trial in order for omega-3 fatty acids to be fully deemed beneficial. Still, seems wonderful that we may have a new tool for dealing with pain associated with aromatase inhibitor use among obese women.

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_________________________

I received an undergraduate degree from Harvard, a medical degree from Yale, and completed a residency in radiation oncology at the University of Pennsylvania. I have been blessed to be named a “top doctor” in Seattle Magazine, US News & World Report, Seattle Metropolitan Magazine, 425 Magazine, and WA magazine. Readers of the Kirkland Advertiser have voted me the top doctor (in any field) in the region. I help individuals with cancer at Evergreen Hospital, outside Seattle. Any information provided herein is not to serve as a substitute for the good judgment of your valued health care provider. Thank you.

Breast Cancer: Do Non-Starchy Vegetables Lower Risk?

Limited evidence suggests that non-starchy vegetables may lower the risk for estrogen-receptor (ER) negative breast cancer, a less common but more challenging to treat type of tumor. Limited evidence also links dairy, diets high in calcium and foods containing carotenoids to lowering the risk of some breast cancers. Carrots, apricots, spinach and kale are all foods high in carotenoids, a group of phytonutrients studied for their health benefits.

The Study: Diet, Nutrition, Physical Activity and Breast Cancer evaluated the research worldwide on how diet, weight and exercise affect breast cancer risk in the first such review since 2010. The report analyzed 119 studies, including data on 12 million women and 260,000 cases of breast cancer.

Results: The report points to links between diet and breast cancer risk. There was some evidence — although limited — that non-starchy vegetables lowers risk for estrogen-receptor (ER) negative breast cancers, a less common but more challenging to treat type of tumor.

Limited evidence also links dairy, diets high in calcium and foods containing carotenoids to lowering risk of some breast cancers. Carrots, apricots, spinach and kale are all foods high in carotenoids, a group of phytonutrients studied for their health benefits.

These links are intriguing but more research is needed, says McTiernan. “The findings indicate that women may get some benefit from including more non-starchy vegetables with high variety, including foods that contain carotenoids,” she said. “That can also help avoid the common 1 to 2 pounds women are gaining every year, which is key for lowering cancer risk.”

Steps Women Can Take: Aside from these lifestyle risk factors, other established causes of breast cancer include being older, early menstrual period and having a family history of breast cancer.

While there are many factors that women cannot control, says Alice Bender, MS, RDN, AICR’s Head of Nutrition Programs, the good news from this report is that all women can take steps to lower their breast cancer risk.

“Wherever you are with physical activity, try to nudge it up a bit, either a little longer or a little harder. Make simple food shifts to boost protection — substitute veggies like carrots, bell peppers or green salad for chips and crackers and if you drink alcohol, stick to a single drink or less,” said Bender.

There are no guarantees when it comes to cancer, but it’s empowering to know you can do something to lower your risk.

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The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

And, one more thing: NEW free apps for Android and iOS (Apple): In apps, search My Breast Cancer by Michael Hunter.

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Reference: S. J. Lowry, K. Kapphahn, R. Chlebowski, C. I. Li. Alcohol Use and Breast Cancer Survival among Participants in the Women’s Health Initiative. Cancer Epidemiology Biomarkers & Prevention, 2016; 25 (8): 1268 DOI: 10.1158/1055-9965.EPI-16-0151

Breast Cancer Local Recurrences Plummeting

This March, I had the pleasure of attending the European Breast Cancer Conference in Barcelona, Spain. While I would like to blog about tapas, the museums (Picasso; Miro; Catalan), the Gothic Quarter and the beach, I will focus today on more quotidian stuff. It is nice to share with you some remarkable progress in the management of early breast cancer. Here is what I heard about:

Women with small, low-grade and well-defined breast cancers that have a tumor gene (genomic) profile that is low have only a 1.4 percent risk of the cancer returning to the site of the original cancer or the nearby lymph nodes within five years, according to new results from a large randomized trial of nearly 7000 patients.

This low risk of locoregional recurrence was seen regardless of whether the women had a mastectomy (the whole breast removed) or breast conserving surgery, in which just the tumour and some surrounding tissue are removed, followed by radiotherapy of the whole breast.

Presenting the latest results from the MINDACT trial at the 11th European Breast Cancer Conference, Professor Emiel Rutgers, a surgeon at the Netherlands Cancer Institute in Amsterdam (The Netherlands), said the findings meant that it was possible to identify women who could safely avoid not only chemotherapy after surgery, but possibly also radiotherapy.

“These findings show that, for these selected women, breast conservation is as good as mastectomy, and the risk of relapse is so low that we should look for ways of giving them less aggressive treatment. For instance, even though radiotherapy reduces the risk of locoregional recurrence two-­ to three-­fold, can we do without it in some selected patients, such as these low risk women, and also in some women aged over 50 with small tumours, less than 2cms in diameter, who have a 1.4% risk of relapse within five years as well,” said Prof Rutgers.

Details, details

Among 6693 patients enrolled in the MINDACT trial, 5470 (82%) underwent breast conserving surgery and 1223 (18%) mastectomy. Decisions on how the women were treated were made  on the basis of the tumour characteristics (size, grade, hormonal and HER2 status, and whether or not the disease had spread to any lymph nodes). In addition, their genetic make-­up was investigated using the 70-­gene-­signature test (MammaPrint®). This analyses the activity of certain genes in early breast cancer and has been shown to accurately predict the risk of the cancer spreading (metastasising) to other parts of the body within five or ten years.

Women who were at low risk of a recurrence, based on these clinical and genomic factors, did not receive chemotherapy after surgery, while those who were at high risk, did. Women with a mixture of high and low risk factors were randomised to receive chemotherapy or not. Almost all women who had breast conserving surgery also had radiotherapy, but not all of the women who had a mastectomy.

In this latest part of the study, Prof Rutgers and his colleagues looked at the rate of locoregional recurrences five years after surgery and analysed them according to the clinical and genetic characteristics. They found that women who had breast conserving surgery had an overall 2.1% risk of recurrence by five years, but if they had a low 70-­gene signature score, the risk dropped to 1.4%, while if they had a high score the risk was 3.6%. Among women who had a mastectomy, the overall risk of recurrence was 2.5%, but this dropped to 0.7% in those with a low genetic score and went up to 4.9% in those with a high score. After full statistical analysis, tumour grade and size were the only factors significantly associated with the risk of locoregional recurrences.

Prof Rutgers said: “The importance of this MINDACT analysis is that local and regional control, in which breast cancer does not come back in the preserved breast, or in the skin after mastectomy, or in the surrounding lymph nodes, is extremely good. The odds of the cancer coming back are about 2% in five years after breast conservation and 2.5% after mastectomy. This includes relapses in the surrounding lymph nodes. This very low risk is determined by the biology of the primary cancer, such as grade, size and growth pattern, and to some extent also by age, with women over 50 years also having a lower overall risk. Among these women aged over 50, those with slow-­growing ‘lazy’ breast cancers have a 0.88% risk, and those with more aggressive ones have a 3.5% risk at five years. We should remember that some 10-­15 years ago a 10% recurrence rate at 10 years was considered the norm.

“Another important message from these findings is that well-­performed breast conserving surgery in women with good indications is as good as mastectomy. Doing a mastectomy when you could very well perform breast conservation will not add a day to the life of a breast cancer survivor. This is a wonderful trial that provides wonderful opportunities for further research.”

I’m Dr. Michael Hunter, and truth be told, immediately after the session’s close, I headed to the Gothic Quarter of Barcelona for churros to dip in rich, smooth and thick dark chocolate. Thanks for joining me today, and if you wish to follow me, please sign up below. Thank you in advance!

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Abstract no: 2 (Best abstract), “Very low risk of locoregional breast cancer recurrence in the EORTC 10041/BIG 03-­04 MINDACT trial: analysis of risk factors including the 70-­gene signature”, closing plenary session, Friday, 15.05-­16.35 hrs, Picasso room.