Best of Breast: news for week ending 7 February 2014

The weekly round-up of breast cancer news from Google Alerts, for the week ending 7 February 2014.

In the past few weeks, animals have been at the forefront of new discoveries in cancer treatments.  We’ve had rats and mice (of course) as they’re always been used for trials, a naked mole rat, and last week a fruit fly.  I didn’t have to hunt far this week:  a woman reported that her Dobermann sniffed out her breast cancer.  It’s one of those stories about the bond between human and pet that makes me go aww…

Doberman

Dog scan: the latest tool in breast cancer detection

Our dogs’ ability to sniff out cancer is nothing new.  I posted about this about a Springer Spaniel who had done the same, in the 30 August edition of Best of Breast this year.  Programmes are now being tested to train dogs to sniff out ovarian cancer.  I’m all for favour of dogs helping us beat this disease, in a non-invasive test.  Wouldn’t it be nice to go to a hospital for a dog scan instead of a Cat scan?

On the more serious side, top billing goes towards French scientists who are using detailed testing of genes to create personalised cancer protocols – if it saves women from unnecessary treatment or overtreatment, that’s fantastic.  Also, more top news:  a modified virus has been developed to fight one of the most challenging of cancers, triple-negative breast cancer.

1.  French scientists take ‘first steps’ towards personalised gene therapy treatment for breast cancer

  • Cancer scientists in France have made “one of the first steps” toward the creation of personalised medicines targeted to combat an individual patient’s breast cancer.
  • By scanning all of the DNA – the entire genome – of more than 400 women with late stage breast cancer for the first time, researchers have provided “proof of principle” that the technique can be used to understand the genetic cause of cancer in an individual, and help design tailor-made drugs to target it.
  • However, the number of patients whose genetic alterations could be “matched” with new treatments was small – only 13 per cent, and experts cautioned that the number of drug trials underway would have to increase if the dream of “precision medicines” for cancer were to become a reality.

“For several years the field of cancer research and treatment has been moving towards the idea of precision medicine – the idea that you take samples of someone’s tumour, you find out the particular molecular faults that are driving it and then you give them the right targeted treatment.

However, there was “an awful long way to go” before the research would yield widespread benefits for patients, adding that complications such as the ability of cancer cells to evolve resistance to even targeted drug treatments would need to be overcome.

For more information:  The Lancet medical journal:  Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER)

2.  Engineered virus to fight triple negative breast cancer

  • In laboratory experiments involving human cancer cells, scientists used a virus similar to the one that helped eradicate smallpox to coax cancer cells to produce a protein which makes them susceptible to radioactive iodine.
  • The scientists successfully infected and killed triple negative breast cancer (TNBC) cells using a vaccinia virus.
  • In addition, the researchers were also able to use the virus to cause infected cancer cells produce a cell surface protein called hNIS that normally is used to concentrate iodine in thyroid cells.
  • The hNIS protein, expressed in thyroid cancer, is why most thyroid cancers can be cured or successfully treated with a small dose of radioactive iodine (which kills thyroid cancer cells expressing hNIS)
  • Armed with the ability to force TNBC cells to produce this protein, researchers now have a way to deliver anticancer therapies to this deadly and resistant form of cancer.
  • The research was conducted by the Department of Surgery at Memorial Sloan-Kettering Cancer Center in New York.

For more information:  http://www.fasebj.org/site/Press_Room/Latest_News.xhtml

Smurf2

Where on earth do they find the names for these gene expressions? Ah well, at least it’s memorable!

3.  Triple-negative breast cancer shows downregulation of Smurf2

  • The HECT family ubiquitin ligase Smurf2 regulates cell polarity, migration, division, differentiation and death, by targeting diverse substrates that are critical for receptor signaling, cytoskeleton, chromatin remodeling and transcription.
  • Recent studies suggest that Smurf2 functions as a tumor suppressor in mice.
  • Studies using quantitative PCR and specific microRNA inhibitors indicated that increased expression of miR-15a, miR-15b, miR-16 and miR-128 was involved in Smurf2 downregulation in those triple-negative cancer cell lines, which have mutations in the retinoblastoma (RB) gene. Forced expression of RB increased levels of Smurf2 protein with concomitant decreases in the expression of the microRNAs.
  • Conclusions: This study provides evidence of posttranscriptional downregulation of Smurf2 in triple-negative breast cancers, and demonstrates that the loss of RB function is involved in microRNA-mediated interference with Smurf2 translation.
  • The new link from RB inactivation to Smurf2 downregulation is likely to play a role in malignant phenotypes of triple-negative breast cancer cells.

For more information:  http://www.biomedcentral.com/1471-2407/14/57/abstract

4.  Age is the main determinant of breast cancer

  • Epigenetics is the study of changes in gene function such as gene expression or gene expression potential – heritable changes passed during cell division – that occur without changes in DNA sequence.
  • A recent study by researchers from the Dartmouth-Hitchcock Norris Cotton Cancer Center (NCCC) examined the connection between cancer and the aging process to see if epigenetic DNA alterations might contribute to age-related increases in breast cancer risk.
  • That is, the study has looked at the connection between cancer and the aging process and has found that DNA alterations contribute to age-related increases in breast cancer risk.
  • The researchers found that age-related changes are present in normal breast tissues of women.
  • However, they were also present and more prominently altered in breast tumors.
  • This means that DNA changes are taking place in a woman’s body as she ages; however, there is also a ‘trigger’ that causes cancer in some people but not in others.
  • Although the aging process has been an implication, scientists still do not know which DNA alterations occur early in carcinogenesis. This is an area of further study.

The study, “Age-related DNA methylation in normal breast tissue and its relationship with invasive breast tumor methylation,” is available online and will appear in the February 2014 issue of Epigenetics.

5.  Post-operative radiotherapy showed limited long-term protection against breast cancer local recurrence

  • Previous trials with long-term follow-up have analyzed the results of lumpectomy and quadrantectomy and concluded that post-operative radiotherapy was associated with reduced recurrence.
  • The purpose of this study was to report the 20-year findings from the Uppsala/Orebro study, which examined women treated by standardized sector resection with or without adjuvant radiotherapy.
  • The research demonstrated that:
  • Post-operative radiation therapy is associated with significantly reduced risk for local recurrence of breast cancer in the first 5 years after primary treatment.
  • However, data suggests that radiotherapy offers no additional protective effect after 5 years of follow-up.

For more information:  Sector Resection With or Without Postoperative Radiotherapy for Stage I Breast Cancer: 20-Year Results of a Randomized Trial

6.  Subtypes of HER2-positive breast cancer with varying sensitivities identified

  • Research has not only shown that human epidermal growth factor receptor 2 (HER2)-positive breast cancer can be classified into four different subtypes, but has also unmasked a subtype showing both a greater response to and increased benefit from chemotherapy and anti-HER2 therapy.
  • The study was led by Aleix Prat, MD, PhD, principal investigator of the Translational Genomics Group at Vall d’Hebron Institute of Oncology (VHIO) in Barcelona, Spain, in collaboration with José Baselga, physician-in-chief of the Memorial Sloan Kettering Cancer Center, New York, New York, and was published in Clinical Cancer Research (2014; doi:10.1158/1078-0432.CCR-13-0239).
  • Such newly refined classification of different tumor subtypes will ultimately facilitate more effective treatment tailored to a specific tumor as well as will advance targeted therapy against HER2-positive breast cancer.

7.  New Data Contradict Current Recommendations for Management of Breast Biopsy Abnormalities in Atypical ductal hyperplasia (ADH) and Atypical lobular hyperplasia (ALH)

  • Previously, many experts believed that ADH leads to low-grade ductal breast cancer in the same breast where the biopsy was done, and so it requires complete surgical excision.
  • Meanwhile, many believed that ALH was simply an indicator of increased risk of breast cancer later in both breasts, so it did not require complete surgical removal but perhaps just closer monitoring.
  • New research challenges that thinking, suggesting that the two types of abnormalities actually behave in similar ways.
  • In the study, nearly 700 women were identified (from a larger group of Mayo patients who’d undergone breast biopsies) who had confirmed abnormal cells but no cancer.
  • While 330 of them had ADH, 327 women had ALH and 32 had both.
  • The researchers followed the women for an average of 12.5 years.
  • During that time, 143 developed breast cancer.
  • A similar number of women with either abnormality developed breast cancer in the same breast within five years, the study found.
  • That suggests that ALH may be both a precursor to cancer and an indicator of increased risk.
  • While some experts believed ALH mostly would lead to lobular cancer, the study found it actually resulted in more ductal cancers, which is how ADH sometimes behaves.
  • The new findings suggest that women with either kind of atypical cells — ductal or lobular — should ask their doctor about closer surveillance and preventive treatment, or chemoprevention (taking anti-cancer drugs to lower the risk).
  • The study was funded by the Mayo Clinic Breast Cancer Specialized Program of Research Excellence, the U.S. National Institutes of Health and the Komen Foundation. One co-author reported a research grant from the drug company Pfizer, and another is a Pfizer consultant.

For more information:  Understanding the Premalignant Potential of Atypical Hyperplasia through Its Natural History: A Longitudinal Cohort Study

8.  Mixed Results for Brachytherapy in Breast Cancer

  • Brachytherapy to the lumpectomy cavity offers certain advantages over EBRT, including convenience and reduced exposure to radiation. Those advantages have fueled rapid growth in use of the treatment in recent years.
  • But some breast cancer specialists have remained unconvinced that breast brachytherapy leads to outcomes comparable to those of EBRT, particularly given the lack of patient-specific evidence to identify the most appropriate candidates.
  • A study has now shown that older breast cancer patients had an increased rate of subsequent mastectomy if they received brachytherapy instead of external-beam radiation therapy (EBRT) after lumpectomy but they fared better than patients who received no radiation, investigators reported.

For more information:  International Journal of Radiation Oncology*Biology Physics, Smith GL, et al “Benefit of adjuvant brachytherapy versus external beam radiation for early breast cancer: Impact of patient stratification on breast preservation”Int J Radiat Oncol Biol Physics 2014; DOI: 10.1016/ijrobp.2013.07.011.

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