Best of Breast: news for week ending 20 December 2013

Updated March 2016 – For more information on GcMAF, please join the GcMAF and GcMAF Cancer forums on Facebook – they are closed groups, so you have to wait for your membership to be confirmed.  They contain up-to-date information on sources of GcMAF, and also feedback and contributions  by people who are using GcMAF.

A round-up of this week’s latest medical developments, culled from Google Alerts.  Again, there’s a glut from the 2013 San Antonio Breast Cancer Symposium, which is no bad thing.

At long last, and about time too:  cancer immunotherapy has been voted breakthrough of the year by Science magazine.  I’m looking forward to the day when all cancers can be prevented and cured by immune-boosting treatments, and cancer vaccines, and not surgery, chemotherapy and radiotherapy

Immunotherapy

image credit:  sciencemagazine.org

Scientists now prove that chemo-brain exists, a fact that people on chemo have known for ages.  Maybe this will mean chemo-brain will be taken seriously and more importantly, some cures will be in the pipeline.

Some interesting research on sugar and its role in cancer – the theory used to be that cancer cells were able to survive without oxygen, by converting sugar directly into energy.  New research has shown that increasing sugar metabolism in cells may be directly responsible for fuelling the growth of cancer cells.

A trial into the use of chemotherapy drug, 5FU (fluorouracil) shows that it did not add to the efficacy of treatment protocols using epirubicin and cyclophosphamide and paclitaxel (FEC +T).  I find this especially relevant because FECT is standard treatment for lymph-node positive breast cancer in the UK.  Does this mean the protocol will change?

Don’t forget to eat your tomatoes – not only is lycopene (the phytochemical contained in them) good for prostate cancer, it has now been shown to have a positive effect on the level of hormones that play a role in regulating fat and sugar metabolism in a trial involving post-menopausal women.

Elsewhere this week is the usual contradictory melange of research – things that work/don’t work:  biphosphonates (drugs that prevent bone loss) work/don’t work.  Macrophages are good/not good depending on the stage of a woman’s menstrual cycle – which makes me wonder if I should be using GcMAF, a supplement that stimulates the production of macrophages?

1.  Immunotherapy voted breakthrough of year by Science magazine

http://news.sciencemag.org/breakthrough-of-the-year-2013

http://www.sciencemag.org/content/342/6165/1432.full

Immunotherapy – a way of fighting cancer that turns the body’s immune cells into targeted tumor killers – was named the breakthrough of the year by the US journal Science today.

Immunotherapy has only worked for a small number of patients, and only in certain cancers, including melanoma and leukemia, but experts believe its promise is huge.

“Oncologists, a grounded-in-reality bunch, say a corner has been turned and we won’t be going back,” said the magazine.

2.  ‘Chemobrain’ Linked to Disrupted Brain Networks

For some cancer patients, the mental fogginess that develops with chemotherapy lingers long after treatment ends. Now, research in breast cancer patients may offer an explanation.
Patients who experience “chemobrain” following treatment for breast cancer show disruptions in brain networks that are not present in patients who do not report cognitive difficulties, according to researchers at Washington University School of Medicine in St. Louis.
The investigators used an imaging technique called resting state functional-connectivity magnetic resonance imaging (rs-fcMRI) to assess the wiring among regions of the brain in 28 patients treated at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University. Fifteen patients reported they were “extremely” or “strongly” affected by cognitive difficulties. The remaining 13 reported no cognitive impairment.
The imaging studies suggest that standard chemotherapy given to breast cancer patients may alter connectivity in brain networks, especially in the frontal parietal control regions responsible for executive function, attention and decision-making.
For more information:

3.  New imaging technique can detect cancer subtypes and early treatment response

http://www.thealmagest.com/new-imaging-technique-can-identify-breast-cancer-subtypes-early-treatment-response/7662

An optical imaging technique that measures metabolic activity in cancer cells can accurately differentiate breast cancer subtypes, and it can detect responses to treatment as early as two days after therapy administration, according to a study published in Cancer Research, a journal of the American Association for Cancer Research.

When they placed normal and cancerous breast cells under the microscope, OMI generated distinct signals for the two types of cells. OMI could also differentiate between estrogen receptor-positive, estrogen receptor-negative, HER2-positive, and HER2-negative breast cancer cells.

Next, the researchers tested the effect of the anti-HER2 antibody trastuzumab on three breast cancer cell lines that respond differently to the antibody. They found that the redox ratios were significantly reduced in drug-sensitive cells after trastuzumab treatment but unaffected in the resistant cells.

They then grew human breast tumors in mice and treated some of these with trastuzumab. When they imaged tumors in live mice, OMI showed a difference in response between trastuzumab-sensitive and -resistant tumors as early as two days after the first dose of the antibody. In comparison, FDG-PET imaging, the standard clinical metabolic imaging technique, could not measure any difference in response between trastuzumab-sensitive and -resistant tumors at any time point in the experiment, which lasted 12 days.

“Cancer drugs have profound effects on cellular energy production, and this can be harnessed by OMI to identify responding cells from nonresponding cells,” said Walsh. “We are hoping to develop a high-throughput screening method to predict the optimal drug treatment for a particular patient.”

Importantly, OMI can be used on tissues freshly excised from patients but, with further development, it could be incorporated in endoscopes for live imaging of human cancers, according to the investigators.

For more information:  American Association for Cancer Research:  http://www.aacr.org/home/public–media/aacr-in-the-news.aspx?d=3183

4.  Cancer deaths rise to 8.2 million, breast cancer sharply up

http://uk.reuters.com/article/2013/12/12/us-cancer-global-idUKBRE9BB0DM20131212

The global death toll from cancer rose to 8.2 million in 2012 with sharp rises in breast cancer  to 522,000 women last year, up 14 percent in the same period, according to the World Health Organisation’s International Agency for Research on Cancer (IARC).

“Breast cancer is also a leading cause of cancer death in the less developed countries of the world,” said David Forman, head of IARC’s Section of Cancer Information, the group that compiles the global cancer data.

He said this was “partly because a shift in lifestyles is causing an increase in incidence, and partly because clinical advances to combat the disease are not reaching women living in these regions.”

5.  First stage of metastasis halted in mice with breast cancer

http://www.sciencecodex.com/first_step_of_metastasis_halted_in_mice_with_breast_cancer-124748

Cell biologists at Johns Hopkins have identified a unique class of breast cancer cells that lead the process of invasion into surrounding tissues. Because invasion is the first step in the deadly process of cancer metastasis, the researchers say they may have found a weak link in cancer’s armor and a possible new target for therapy. A summary of their results will be published online in the journal Cell on Dec. 12.

Looking for a molecular cause for the apparent “leadership” seen in the initiating cells, scientists searched for proteins that were uniquely present in the leader cells. They identified one protein, cytokeratin 14, or K14, that was present in almost all leader cells but was very rare in the noninvasive parts of the tumor. When the team looked at tumors from mice that had other types of breast cancer — some more prone to invasion and others less prone — all had leader cells containing K14. The more invasive a tumor was, the more cells with K14 it had.

For more information:  http://www.hopkinsmedicine.org/news/media/releases/first_step_of_metastasis_halted_in_mice_with_breast_cancer

6A.  Role of sugar uptake in breast cancer revealed

Mina Bissell, distinguished scientist with Lawrence Berkeley National Laboratory (Berkeley Lab)’s Life Sciences Div. and a leading authority on breast cancer, has shown that aerobic glycolysis is not the consequence of the cancerous activity of malignant cells but is itself a cancerous event.

“In a series of papers published in the early 1970s, using fibroblasts from chick embryos and their malignant counterparts, we showed that if the microenvironmental context was equalized, the rate of aerobic glycolysis was indeed higher in cancer cells under all conditions tested,” Bissell says. “Clearly Warburg was correct in saying that cancer cells always had increased aerobic glycolysis; however, he was not necessarily correct in saying that the defect had to be in respiratory pathways. We found these pathways to be similarly active in normal and malignant fibroblasts, as we find also now in our breast cancer cell studies in 3-D assays.”

“A dramatic increase in sugar uptake could be a cause of oncogenesis,” Bissell says. “Furthermore, through a series of painstaking analysis, we have discovered two new pathways through which increased uptake of glucose could itself activate other oncogenic pathways. This discovery provides possible new targets for diagnosis and therapeutics.”

“We found that overexpression of GLUT3 in the non-malignant human breast cells activated known oncogenic signaling pathways and led to the loss of tissue polarity and the onset of cancerous growth,” Bissell says. “Conversely, the reduction of GLUT3 in the malignant cells led to a phenotypic reversion, in which the oncogenic signaling pathways were suppressed and the cells behaved as if they were non-malignant even though they still contained the malignant genome.”

For more information:

Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways

6B.  New findings give clues to why breast cancer is more common in people with diabetes

In the human tissue, the researchers found levels of glucose transport protein, GLUT3, was 400 times higher in malignant (cancer that’s likely to spread) cells than non-malignant cells. The role of GLUT3 is to allow glucose to pass through the membranes of cells. In cancer, this can be significant as uptake of glucose provides new cancerous cells with the energy to grow.

The research is significant in two ways as it may offer clues as to why breast cancer has been shown to be more common in women with type 2 diabetes, and it may also reveal clues as to how breast cancer may be treated in people with or without diabetes.

Research to date has shown significant promise for diabetes medications, notably including metformin, to have anti-cancer properties.

7.  Diet rich in tomatoes may lower breast cancer risk

http://www.sciencecodex.com/diet_rich_in_tomatoes_may_lower_breast_cancer_risk-125122

A tomato-rich diet may help protect at-risk postmenopausal women from breast cancer, according to new research accepted for publication in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.

Breast cancer risk rises in postmenopausal women as their body mass index climbs. The study found eating a diet high in tomatoes had a positive effect on the level of hormones that play a role in regulating fat and sugar metabolism.

The longitudinal cross-over study examined the effects of both tomato-rich and soy-rich diets in a group of 70 postmenopausal women. For 10 weeks, the women ate tomato products containing at least 25 milligrams of lycopene daily. For a separate 10-week period, the participants consumed at least 40 grams of soy protein daily. Before each test period began, the women were instructed to abstain from eating both tomato and soy products for two weeks.

The soy diet was linked to a reduction in participants’ adiponectin levels. Researchers originally theorized that a diet containing large amounts of soy could be part of the reason that Asian women have lower rates of breast cancer than women in the United States, but any beneficial effect may be limited to certain ethnic groups, Llanos said.

For more information:  https://www.endocrine.org/news-room/current-press-releases/diet-rich-in-tomatoes-may-lower-breast-cancer-risk

8.  I-SPY-2:  A new way of speeding up the testing of breast cancer drugs using statistical techniques

http://www.daily-chronicle.com/2013/12/14/new-drug-study-method-show-breast-cancer-promise/a9vm8bg/

A novel way to speed the testing of cancer drugs and quickly separate winners from duds has yielded its first big result: an experimental drug, veliparib, that shows promise against a hard-to-treat form of breast cancer.

The method involves studying drugs in small groups of people and using advanced statistical techniques to analyze the results as they come in, instead of waiting for all the data to arrive.

Bringing a new cancer drug to market usually takes more than a decade and tests in thousands of patients, and costs more than $1 billion. Companies can’t afford many studies like that, and patients can’t wait years for potentially life-saving new medicines, said Don Berry, a biostatistician at the University of Texas MD Anderson Cancer Center.

The study, called I-SPY 2, puts small groups of women on experimental drugs or combinations, then gives them surgery to see what effect the medicines had. The best result is a complete response, where no signs of cancer remain.

Each patient’s results are analyzed as they come in, and advanced statistical methods are used to calculate probabilities that the drug would help in various situations, depending on which women had a complete response.

“This allows us to learn and adapt from each patient as the study goes on,” and results on early participants guide treatment that later ones get, said Dr. Hope Rugo of the University of California, San Francisco. When enough evidence indicates a high probability of success, the drug “graduates” to final-phase testing.

The results show that “we can get early reads on something that is worth pursuing” and bail quickly on treatments that don’t help, said Dr. Carlos Arteaga of the Vanderbilt-Ingram Comprehensive Cancer Center.

For more information:

I-SPY2 trial: http://www.ispy2.org

Cancer meeting: http://www.sabcs.org

9.  Cancer cells fused with macrophages play a key role in metastasis

http://www.news-medical.net/news/20131216/Cancer-cells-that-fuse-with-macrophages-play-key-role-in-the-spread-of-cancer.aspx?page=2

Cancer cells that spontaneously fuse with macrophages, the immune system’s healthy scavenger cells, play a key role in the metastasis, or spread of the cancer to other areas of the body, according to research to be presented Sunday, Dec. 15, at the American Society for Cell Biology annual meeting in New Orleans.

The researchers, Alain Silk, Ph.D., Melissa Wong, Ph.D., and colleagues at Oregon Health & Science University (OHSU) in Portland followed the work of German pathologist Otto Aichel, who suggested in 1911 that a cancer cell under attack by a white blood cell might spontaneously fuse with that cell to produce a hybrid cell with chromosomal abnormalities that could lead to cancer.

Although Aichel’s theory was dismissed by his contemporaries, recent discoveries about the broader role of cell fusion in tissue homeostasis and regeneration have revived scientific interest in his ideas. Today there is strong evidence of fusion between cancer and normal cells in human cancer, but it has not been apparent whether cell fusion could provide cancer cells with a selective advantage that enhances cancer progression.

SOURCE American Society for Cell Biology

10.  Macrophages open window to breast cancer risk

http://yottafire.com/2013/12/immune-cells-open-window-breast-cancer-risk/

University of Adelaide researchers have made a major discovery that highlights the important role played by immune cells in the risk of developing breast cancer.

Researchers have focused their efforts on immune cells known as macrophages in the breast, and how the role of these cells changes because of fluctuations in hormones during different times of the month.

The results of laboratory studies – published online ahead of print in the journal Biology of Reproduction – show that while the immune cells have a role to play in the normal function of the breast, at certain stages in the menstrual cycle they may help to make the breast more susceptible to cancer.

“These cells should be protecting our body from cancer, but at certain times of the month it appears macrophages might be allowing cancerous cells to escape immune system detection,” says the lead author of the study Wendy Ingman, who is The Hospital Research Foundation Associate Professor of Breast Cancer Research / National Breast Cancer Foundation Early Career Fellow.

“It’s sort of a Jekyll and Hyde scenario – we need the macrophages to do their job so that the breast can function normally, but at the same time they’re giving cancerous cells the chance to survive.

“We think there is a window of risk that opens up around the time when women have their period. This is when levels of the hormone progesterone drop, and this affects how the breast functions. At this time, immune defenses in the breast tissue are down and women could be more susceptible to the initiating factors that lead to breast cancer,” she says.

For more information:  http://www.adelaide.edu.au/news/news64882.html

Biology of Reproduction:  Macrophage Phenotype in the Mammary Gland Fluctuates over the Course of the Estrous Cycle and Is Regulated by Ovarian Steroid Hormones

11.  Bisphosphonates Useful in Older Women With Breast Cancer

Use of bisphosphonates benefits postmenopausal women with breast cancer the most, a meta-analysis that scrutinized outcomes in 17,000 breast cancer patients suggests.

Among 1,1036 postmenopausal women selected from a meta-analysis, 21.9% experienced distant recurrences of breast cancer if they were not on bisphosphonate therapy compared with 18.4% of women who were taking bisphosphonates — a 3.5% difference that was highly statistically significant (P=0.0003), according to Robert Coleman, MBBS, MD, professor of medicine at the University of Sheffield in Sheffield, England, reported at the annual San Antonio Breast Cancer Symposium

12.  Bisphosphonate zoledronate treatment not effective in women with chemoresistant breast cancer

Treatment with the bisphosphonate zoledronate did not improve outcomes for women with chemoresistant breast cancer, according to initial results of a phase III clinical trial presented here at the 2013 San Antonio Breast Cancer Symposium, held Dec. 10-14.

Many patients with breast cancer are treated with chemotherapy prior to surgery. In some patients who receive this form of treatment, which is called neoadjuvant therapy, no residual invasive cancer can be detected in breast tissue samples and lymph nodes removed during surgery. Patients with residual disease are considered to have breast cancer that is resistant to chemotherapy, and emerging data indicate that they experience poorer long-term outcomes compared with women who respond completely to neoadjuvant therapy.

“Because patients with residual disease after neoadjuvant chemotherapy are considered to have chemoresistant breast cancer, they have few postsurgery treatment options,” said Gunter von Minckwitz, M.D., Ph.D., chairman of the German Breast Group in Neu-Isenburg, Germany. “We evaluated a new postsurgery treatment for these patients, the bisphosphonate zoledronate, in a phase III clinical trial.

“We are disappointed to report that zoledronate had no effect on event-free survival. That is, it had no effect on the number of patients who had disease relapse, developed a new cancer, or died.Although the results are completely negative, we hope that our experience running the first phase III clinical trial to test a treatment in women who had not had a complete response to neoadjuvant therapy will inform future post-neoadjuvant phase III clinical trials,” added von Minckwitz, who is also professor of gynecology at the University of Frankfurt.

For more information:

Primary source: San Antonio Breast Cancer Symposium
Source reference: Coleman R, et al “Effects of bisphosphonate treatment on recurrence and cause-specific mortality in women with early breast cancer: A meta-analysis of individual patient data from randomised trials” SABCS 2013; Abstract S4-07.

Additional source: San Antonio Breast Cancer Symposium
Source reference:von Minckwitz G, et al “Postneoadjuvant treatment with zoledronate in patients with tumor residuals after anthracyclines-taxane-based chemotherapy for primary breast cancer – The phase III NATAN study (GBG 36/ABCSG XX)” SABCS 2013; Abstract S5-05.

13.  Leukemia Drug With Letrozole Slows Metastatic Breast Cancer

http://www.medscape.com/viewarticle/817784

The addition of the leukemia drug dasatinib (Sprycel, Bristol-Myers Squibb and Otsuka America) to the aromatase inhibitor (AI) letrozole as first-line treatment for HER2-negative metastatic breast cancer in postmenopausal women improved progression-free survival but not the clinical benefit rate, compared with letrozole alone, new research shows.

Results from the phase 2 study were reported at the 36th Annual San Antonio Breast Cancer Symposium.

14.  Ramucirumab plus docetaxel did not delay breast cancer progression

http://www.healio.com/hematology-oncology/highlights-from-sabcs-2013/ramucirumab-plus-docetaxel-did-not-delay-breast-cancer-progression

 The combination of ramucirumab and docetaxel failed to halt advanced breast cancer progression in HER-2–negative tumors, according to research presented at the San Antonio Breast Cancer Symposium.

For more information:
Mackey JR. Abstract #S5-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-14, 2013; San Antonio.

15.  Breast Cancer: Tamoxifen Metabolite Promising

http://www.medpagetoday.com/MeetingCoverage/SABCS/43445

In the first human experience with a drug that is the main metabolite of tamoxifen, promising responses were observed in woman diagnosed with aromatase inhibitor resistant, metastatic breast cancer, researchers presented at the 2013 San Antonio Breast Cancer Symposium.

In an animal model of a letrozole resistant xenograft, endoxifen appeared superior to tamoxifen, exemestane and exemestane plus everolimus (RAD001). “The reasons for the superior antitumor activity of endoxifen appears to be complex, and related to the fact that endoxifen is a more potent anti-estrogen, does not activate critical oncogenes involved in nongenomic signaling and may inhibit other kinases.”

Primary source: San Antonio Breast Cancer Symposium
Source reference: Goetz M, et al “Title: A first-in-human phase I study of the tamoxifen metabolite, Z-endoxifen hydrochloride in women with aromatase inhibitor refractory metastatic breast cancer (NCT01327781)” SABCS 2013; Abstract PD3-4.

16.  Doubling dose of Faslodex extended life with Advanced Breast Cancer

http://www.dailyrx.com/faslodex-extended-overall-survival-women-advanced-or-metastatic-breast-cancer

Most breast cancers are fueled by the hormone estrogen, and a number of medications are made to block the production of estrogen. A recent trial assessed one such medication in treating advanced breast cancer.

 This international trial found that women with advanced estrogen receptor-positive breast cancer who were given 500 mg of Faslodex (fulvestrant) lived longer than those who received 250 mg of the medication.

The medicine was well tolerated by the women in both groups, and there were no serious side effects or safety concerns, according to the researchers.

17.  Carboplatin in combination with Avastin shows promise for women with triple-negative breast cancer

http://www.sciencecodex.com/additional_drug_shows_promise_for_women_with_triplenegative_breast_cancer-124837

In a nationwide study of women with “triple-negative” breast cancer, adding the chemotherapy drug carboplatin or the angiogenesis inhibitor Avastin to standard chemotherapy drugs brought a sharp increase in the number of patients whose tumors shrank away completely, investigators will report at the 2013 San Antonio Breast Cancer Symposium.

The results are especially promising in the case of carboplatin, study leaders say, as Avastin has shown little effectiveness as a long-term preventer of cancer recurrence.

Patients with triple-negative tumors had an estimated pathologic complete response (pCR) rate of 52% with the PARP inhibitor veliparib plus carboplatin followed by conventional chemotherapy versus 26% with conventional chemotherapy alone. The regimen has a 99% probability of superiority versus chemotherapy alone and a 90% probability of success in a planned 300-patient clinical trial.

Primary source: San Antonio Breast Cancer Symposium
Source reference: Rugo HS, et al “Veliparib/carboplatin plus standard neoadjuvant chemotherapy for high-risk breast cancer: First efficacy results from the I-SPY 2 trial”SABCS 2013; Abstract S5-02.

18.  RINT1 gene variants also may play role in other cancers

http://www.thealmagest.com/mutations-novel-tumor-suppressor-gene-associated-early-onset-breast-cancer/7217

An international team of scientists has identified an association between heritable, rare mutations in the RINT1 gene and increased risk of early onset breast cancer, according to research reported at the American Society of Human Genetics 2013 annual meeting in Boston.

The rare mutations in RINT1, a tumor suppressor gene, were detected in three of 49 families participating in a study that sequenced the whole exome, the protein-coding DNA, of families with multiple individuals affected by breast cancer.

19.  5-FU Strikes Out in Early-Stage Breast Cancer

http://www.medpagetoday.com/MeetingCoverage/SABCS/43461

A widely used chemotherapy drug offers no benefit when added to standard treatment for early-stage, node-positive breast cancer, a researcher said here.

In a large phase III trial, adding fluorouracil (5-FU), did not improve either invasive disease-free survival (DFS) or overall survival (OS), according to Francesco Cognetti, MD, of the Regina Elena National Cancer in Rome.

On the other hand, an accelerated, or dose-dense, standard regimen led to significant increases in both endpoints, Cognetti reported at the annual San Antonio Breast Cancer Symposium.

But the key finding, Cognetti said, was that “5-FU should be deleted” from anthracycline-taxane combinations used after surgery for node-positive cancer.

The study, dubbed GIM-2, tested a regimen of epirubicin and cyclophosphamide — with or without 5-FU — followed by paclitaxel. The regimens were given in either 3-week or 2-week cycles, so that patients were studied in one of four arms.

In the U.S., he said, many centers have already stopped using the drug in combination with epirubicin and cyclophosphamide, he told MedPage Today.

For more information:

Primary source: San Antonio Breast Cancer Symposium
Source reference: Cognetti F, et al “Epirubicin and cyclophosphamide (EC) followed by paclitaxel (T) versus fluorouracil, epirubicin and cyclophosphamide (FEC) followed by T, all given every 3 weeks or 2 weeks, in node-positive early breast cancer (BC) patients (pts). Final results of the gruppo Italiano mammella (GIM)-2 randomized phase III study” SABCS2013; Abstract S5-06.

20.  Radiotherapy for Breast Cancer doesn’t have much impact on survival for women 65 years old and above

http://www.hngn.com/articles/19510/20131213/radiotherapy-for-breast-cancer-doesn-t-have-much-impact-on-survival.htm

Researchers from the University of Edinburgh led by Prof. Ian Kunkler, who is also consultant in Clinical Oncology, found that radiotherapy for low-risk breast cancer patients who are 65 years old and above has minimal impact on the recurrence with no apparent survival impact.

Their study showed that in a five-year period, the local recurrence had low levels for both who received radiotherapy and those who did not, with 1.3 percent with radiation and 4.1 percent without it.

For more information:

American Society of Human Genetics:  Mutations in novel tumor suppressor gene associated with early onset breast cancer and possibly other cancers

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