Best of Breast: news for week ending 13 June 2014

The weekly round-up of news from the world of Breast Cancer and Cancer from Google Alerts, for the week ending 13 June 2014.

The ASCO 2014 may be over, but there’s still a glut of news.

I wanted to highlight the first item which suggests that breast cancer survivors don’t get enough exercise with a humorous cartoon showing what women with breast cancer are busy getting on with life and the housework and kids to set aside time for the gym.  In a previous post, there was an article which implied that housework counted as exercise – I think all researches should take this into consideration.

There’s an interesting study on limiting carbs to improve survival, which could be an argument for either a low-carb or even the more extreme ketogenic diet.

A lot of breast cancer research is done on mice and rats.  A study shows that this may not be the best method as there are similarities and differences between rodents and humans which may make rodent trials an ineffective way of testing treatments.


Breast cancer survivors do not exercise enough. (With thanks to KS for this!)

1.  Breast cancer survivors ‘do not exercise enough’

  • Exercise can aid recovery after breast cancer but many women are not active enough, a study suggests.
  • Being active is known to be beneficial but US researchers, writing in the journal Cancer, said they had found many women did too little.
  • Only a third met recommended activity levels.
  • UK breast cancer groups said women here also needed more support to keep active after having the disease.
  • In the US and the UK, adults are recommended to do at least 150 minutes of moderate-intensity physical activity or 75 minutes of vigorous-intensity physical activity each week.
  • But this study found only 35% of women who had experienced breast cancer met the physical activity guidelines.

For more information: Cancer, DOI: 10.1002/cncr.28630, Racial differences in physical activity among breast cancer survivors: Implications for breast cancer care

Also read:

2.  Limiting carbs could reduce breast cancer recurrence in women with positive IGF1 receptor

  • Dartmouth researchers have found that reducing carbohydrate intake could reduce the risk of breast cancer recurrence among women whose tumor tissue is positive for the IGF-1 receptor.
  • “There is a growing body of research demonstrating associations between obesity, diabetes, and cancer risk.
  • “There are similarities between the biological pathways that underlie all of these conditions, and there is some evidence to suggest that over-activation of the insulin/insulin-like growth factor axis, which increases the availability of IGF1 in the blood, may relate to a poor prognosis among breast cancer survivors.”
  • Receptors for IGF1 have been found in breast tumor tissue, and expression of those receptors may contribute to treatment resistance among breast cancer survivors.
  • Since diet can influence insulin activation, the researchers wondered whether diet could impact breast cancer prognosis based on expression of the IGF1 receptor in the primary breast tumor tissue.
  • This is the first study to suggest that it might be possible to personalize recommended diets for breast cancer survivors based on the molecular characteristics of their primary tumor.
  • Further research is needed to confirm these findings, and researches note that breast cancer survivors should not be concerned about dramatically lowering their carbohydrate intake based on this study.
  • “There are still many unanswered questions regarding this study, including what type of carbohydrate-containing foods may be the most important foods that breast cancer survivors should limit.”

The study, “Risk of Breast Cancer Recurrence Associated with Carbohydrate Intake and Tissue Expression of IGFI Receptor,” will appear in the July issue of Cancer Epidemiology Biomarkers & Prevention.

Cancer Epidemiol Biomarkers Prev. 2014 Apr 22. [Epub ahead of print], Risk of Breast Cancer Recurrence Associated with Carbohydrate Intake and Tissue Expression of IGFI Receptor

3.  Immune T-cells found near tumours boost breast cancer survival

  • WOMEN with breast cancer are 10 per cent more likely to survive for five years or more if they have killer T-cells near their tumours.
  • The Cancer Research UK study* found that when these immune cells were present, survival improved for women with ER-negative and ER-positive HER2-postive breast cancer.
  • However, survival didn’t change for women with ER-positive HER2-negative breast cancer.
  • “This important insight could help doctors personalise a woman’s treatment based on her immunological profile and also suggests that new treatments should harness the immune system to fight cancer.”

For more information:  Annals of Oncology 00: 1–8, 2014  doi:10.1093/ annonc/mdu191,  Association between CD8+ T-cell infiltration and breast cancer survival in 12 439 patients


Image credit: Harvard Medical School News

4.  Mice Can Mimic Human Breast Cancer at Gene Level

  • Scientists have routinely used mice to replicate aspects of human breast cancer in an effort to find a cure to the most common type of cancer among women.
  • But how effective are these preclinical models in actually mimicking the disease and giving scientists the ability to develop real comparisons?
  • Eran Andrechek, a physiology professor in the College of Human Medicine at Michigan State Univ., has discovered that many of the various models used in breast cancer research can replicate several characteristics of the human disease, especially at the gene level.
  • Careful consideration is important because not all models can replicate the same diversities found in breast cancer.
  • One strain may show likenesses in the appearance of tumors, while others may have similarities in genes that are turned on.
  • Yet none of the models may be effective in demonstrating the way the cancer signals to other cells that tell the disease to grow.
  • The research highlights the ways these models should be used to study the disease and Andrechek’s new database could prove to be a valuable resource to researchers around the world.
  • “There are definitely clear parallels between mice and men in relation to breast cancer and this study provides legitimacy to using these models so ultimately a cure can be found,” he says.

For more information:  Breast Cancer Research 2014, 16:R59 doi:10.1186/bcr3672, A genomic analysis of mouse models of breast cancer reveals molecular features of mouse models and relationships to human breast cancer

And if you’re really interested, check out:

5.  Cholesterol drug plus radiotherapy improves outcome for women with inflammatory breast cancer

  • Patients with inflammatory breast cancer could potentially benefit by supplementing radiation treatments with a generic, low-cost medication commonly prescribed to treat high cholesterol
  • “Our study showed for the first time that simvastatin combined with radiation improved the local recurrence-free survival rate of women with inflammatory breast cancer (IBC), an aggressive variant of breast cancer with a dismal prognosis,”
  • IBC’s propensity to metastasize – that is, spread from one part of the body to another and form secondary tumors — might be due to the migration of surviving cancer stem cells that have developed a resistance to both radiation and chemotherapy.
  • Large retrospective studies from Denmark recently rekindled the interest of the scientific community in how statins affect breast cancer.
  • Statins, which have been used since the 1980s, have a well-described safety and toxicity profile and are commercially available in generic forms.
  • While they are mainly prescribed to treat high cholesterol, they also seem to combat IBC stem cells’ resistance to treatment in several ways, including by inhibiting two proteins key to tumor development.

For more information:  Stem Cells Translational Medicine, doi:10.5966/sctm.2013-0204, Simvastatin Radiosensitize Differentiated and Stem-Like Breast Cancer Cell Lines and Is Associated With Improved Local Control in Inflammatory Breast Cancer Patients Treated With Postmastectomy Radiation

6.  Breast cancer survival improved when radiotherapy guidelines followed

  • A retrospective study confirmed that adherence to consensus guidelines for adjuvant radiotherapy (RT) in the treatment of patients with primary breast cancer improves survival.
  • The resultsrevealed that patients who received international guideline-adherent adjuvant RT (GAART) had significantly improved rates of survival compared with patients who did not receive GAART.
  • The study also showed, however, that GAART does not compensate for an incomplete tumor resection.
  • The authors found no significant difference between patients who received BCS followed by GAART and patients who received mastectomy without RT.
  • Overtherapy (i.e., RT performed but not guideline adherent) did not improve OS or RFS.

For more information:  Ann Oncol (2014) 25 (3):628-632, doi:10.1093/annonc/mdt584, The impact of adjuvant radiotherapy on the survival of primary breast cancer patients: a retrospective multicenter cohort study of 8935 subjects

7.  Blocking STAT5 protein reduce side effects and need for ongoing therapy in leukemia

  • The study examined how blocking certain proteins might affect the death of cancerous cells, a subject that researchers said was ‘poorly understood’.
  • The researchers found that blocking a protein named STAT5 proved lethal for chronic myeloid leukemia (CML) cells, and the findings extend beyond CML to all targeted cancer treatments.
  • The activity of STAT5 appears to be a critical determinant of the decision for cancer cells to live or die.
  • ‘Our research has found that by blocking STAT5 in conjunction with exposure to a regular anti-cancer treatment, we were able to more effectively target the leukaemia cells. We now also better understand the timing required for the combined treatment to be effective.’

For more information:  Leukaemia, doi: 10.1038/leu.2014.156, Sustained inhibition of STAT5, but not JAK2, is essential for TKI-induced cell death in chronic myeloid leukemia

8.  Blocking p110delta enzyme boosts body’s immune response against cancer

  • Cancer suppresses the immune system by producing an enzyme called ‘p100delta’ which tells it to power down, making it difficult for the body to fight the disease.
  • ‘Delta-inhibitors’ were already known to help leukaemia patients, but researchers were amazed to find they also work on a whole range of other cancers.
  • Now, scientists at UCL and the Babraham Institute in Cambridge, have discovered that the same ‘delta inhibitors’ are also effective against lung, pancreatic, skin and breast cancers, and probably many more.
  • The drugs, which are taken orally as a pill, were so successful in leukaemia trials that the control group, who were taking placebos, were immediately switched to the medication on ethical grounds.
  • The drugs, which are taken orally as a pill, were so successful in leukaemia trials that the control group, who were taking placebos, were immediately switched to the medication on ethical grounds.
  • Although the study was conducted in mice, researchers are confident it would work in humans and are hopeful that human trials will begin soon.
  • Mice given the drug survived breast cancer for almost twice as long.
  • Their cancers also spread significantly less, with far fewer and smaller tumours developing.
  • Survival after surgical removal of primary breast cancer tumours was also vastly improved, which has important clinical implications for stopping breast cancer from returning following surgery.
  • And they discovered that the immune system ‘remembers’ the cancer and can fight it off completely again. Mice who were given cancer a second time all survived.

For more information:  Nature, 510, 407–411 (19 June 2014) doi:10.1038/nature13444, Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer

9.  Can breast cancer risk be predicted by skin moles?

  • PLOS Medicine has simultaneously published two new studies finding that moles – or cutaneous nevi – may be a predictor of breast cancer.
  • The two teams – from the US and France – find that women with a greater number of moles are more at risk of developing breast cancer.
  • Some studies have shown that women with a greater number of moles are more at risk from hormone-influenced conditions such as endometriosis, leiomyoma and thyroid diseases.
  • The number of moles that a person might acquire – as well as melanoma risk – has also been associated with the CDKN2A gene.
  • Inactivation of this gene – which is implicated in cell cycle regulation – is associated with breast cancer.
  • French researchers‘ investigations showed that Women reporting having “very many” moles were found to have a 13% higher risk of breast cancer than women reporting having no moles.
  • However, when the results were adjusted for known breast cancer risk factors, the association was no longer statistically significant. These confounding risk factors – such as benign breast disease or family history of breast cancer – are themselves associated with mole number.
  • American researchers‘ analysis of research found that women reporting 15 or more moles were 35% more likely to be diagnosed with breast cancer than those reporting no moles.
  • From this, they calculated that women with 15 or more moles had an absolute risk of 11.4% of developing breast cancer, compared with an absolute risk of 8.48% in women with no moles.
  • Although both studies found an association between breast cancer and number of moles, neither study was able to clearly identify the mechanism that drives this association.

For more information:  Plos Medicine, DOI: 10.1371/journal.pmed.1001659, Association between Cutaneous Nevi and Breast Cancer in the Nurses’ Health Study: A Prospective Cohort Study AND DOI: 10.1371/journal.pmed.1001661, Melanocytic Nevi as Biomarkers of Breast Cancer Risk

10.  Breast Cancer Drug Herceptin Linked to Risk of Heart Problems: Study

  • Herceptin is used in breast cancers that test positive for HER 2 (human epidermal growth factor receptor 2), which promotes the growth of cancer cells.
  • Herceptin kills the cells, and is known to boost survival, both in those with breast cancer that has spread and to those with HER2-positive early breast cancer. It’s given after primary treatments for breast cancer, such as surgery, chemotherapy and radiation.
  • As many as one in 10 women taking the breast cancer drug trastuzumab (Herceptin) will experience some type of heart problem, according to new research.
  • The good news from this study is that these problems typically reverse once treatment is finished.
  • The study authors don’t know for sure why the drug is associated with heart issues, but they noted that HER2 is linked with the regulation of cell growth and survival in the heart. Using the drug may take away those heart protective effects.
  • Roche, the maker of Herceptin, provided research funding. Some of the study’s co-authors work for Roche or are advisers or consultants.

For more information:  Journal of Clinical Oncology online, June 9, 2014, doi:10.1200/ JCO.2013.53.9288, Trastuzumab-Associated Cardiac Events at 8 Years of Median Follow-Up in the Herceptin Adjuvant Trial (BIG 1-01)

11.  Some Triple Negative Breast Cancer Patients May Benefit from Immunotherapy

  • The study found that a cohort of triple negative breast cancer patients had high expression of PD-L1 (program death ligand) and other immune regulators such as CTLA-4 (Cytotoxic T-lymphocyte Antigen) and IDO-1 (indoleamine 2,3-dioxygenase).
  • High PD-L1 expression was found in patients whose tumors were triple negative and androgen receptor negative.
  • High PD-L1 expression was related to DNA repair gene abnormalities including BRCA1.
  • PD-L1 has been associated with response to immunotherapy.
  • The finding that BRCA1 mutation carriers may be good candidates for immunotherapy is exciting and unexpected.
  • In the past patients with BRCA1 and triple negative breast cancer were found to have lymphocytic infiltration into their tumors.
  • Now we see that there may be a reason for this – the DNA instability found in these tumors.
  • This could mean that patients with BRCA1 mutations would benefit from immunotherapy.

For more information:  Abstract presented at 2014 American Society of Clinical Oncology in Chicago, Abstract No: 1001, Expression of novel immunotherapeutic targets in triple-negative breast cancer., J Clin Oncol 32:5s, 2014 (suppl; abstr 1001)

12.  Two new possible drug targets for triple negative breast cancer

  • The suppression of two genes reduces breast cancer tumor formation and spread by interfering with blood vessel formation and recruitment, according to new research from Houston Methodist, Weill Cornell Medical College and other institutions.
  • The findings in the Proceedings of the National Academy of Sciences may help medical researchers identify effective drug targets for triple negative breast cancer (TNBC).
  • The genes, MLF2 (myeloid leukemia factor 2) and RPL39 (a ribosomal protein), were found to most profoundly affect the production of nitric oxide synthase, which helps regulate blood vessel behavior and could be crucial to the recruitment of new blood vessels to growing tumors.
  • These genes influence the spread of TNBC throughout the body, and have not so far been linked with breast cancer.
  • The researchers went a step further, determining which configurations of small inhibitory RNA (siRNA) were most efficient at shutting down MLF2 and RPL39 in breast cancer stem cell lines.
  • siRNA molecules interfere with the cell’s ability to express genes and have proven to be effective drug tools for a wide variety of diseases, including some cancers.
  • In preliminary studies, the combination of siRNA and chemotherapy agent docetaxel significantly reduced tumor volume relative to chemotherapy alone and also appeared to prolong survival.
  • Separate analyses showed suppression with siRNA appeared to yield fewer metastases to lung tissue.

For more information:  Proceedings of the National Academy of Sciences, doi: 10.1073/pnas.1320769111, Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer by inhibiting nitric oxide synthase signaling

13.  Hunting down the Her3 receptor using PET

  • For years researchers have been developing molecular imaging techniques that visualize hormonally active breast cancer cells—specifically those testing positive for human epidermal growth factor receptor 2 (HER2).
  • A recent innovation in breast cancer biomarkers seeks the HER3 receptor instead, which could mean more comprehensive breast cancer imaging and potential treatments, say experts presenting data during the Society of Nuclear Medicine and Molecular Imaging’s 2014 Annual Meeting.
  • “HER3 is thought to be an important mediator of resistance to the HER2 inhibitors class of anti-cancer therapies, which are used to treat HER2-positive breast cancer representing approximately 20 percent of all breast cancers,” said principal author Eric P. Wehrenberg-Klee, MD, from Massachusetts General Hospital in Boston, Mass.
  • “Imaging of HER3 expression may allow for better understanding of how prevalent HER3 over-expression is among HER2 positive breast cancer patients, which in turn may allow for appropriate patient selection for the addition of HER3 inhibitors currently in clinical development.”
  • Researchers developed an antibody-based PET probe specific for HER3, characterized it in vitro in a panel of HER3 expressing breast cancer cell lines, and performed in vivo PET-CT imaging in mouse xenografts
  • The researchers expect that it may be another year or two before the agent will reach regulatory approval and enter general clinical practice.

For more information:  The Journal of Nuclear Medicine, “Development of a HER3 PET probe for breast cancer imaging,” SNMMI’s 61th Annual Meeting, June 7–11, 2014, St. Louis, Missouri.

14.  Researchers study why older women are more vulnerable to breast cancer

  • Scientists from the Lawrence Berkeley National Laboratory have revealed clues to why older women are more vulnerable to breast cancer.
  • As women age, cells in their epithelial breast tissue become less responsive to their environments, diminishing their ability to identify and fight tumors.
  • The researchers placed multipotent progenitors, a type of cell found in breast tissue, in environments of varying “stiffness” that could be experienced in a breast, to determine the variation in response based on a woman’s age.
  • “In the young women, there might be a defensive mechanism. When the tissue stiffens to be more like a tumor, the normal healthy tissue responds.  In older women, they’re losing that tumor-suppressive reaction.”
  • The differences between the cells of older and younger women are assumed to be due to “global changes in gene expression patterns” that occur during the aging process.  The scientists now aim to study how and why these patterns change in the aging process.

For more information:  Cell Reports (2014), 10.1016 /j.celrep. 2014.05.021, Age-Related Dysfunction in Mechanotransduction Impairs Differentiation
of Human Mammary Epithelial Progenitors


Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )


Connecting to %s