Best of Breast: news for week ending 6 June 2014

The weekly aggregation from Google Alerts, for articles on Breast Cancer and Cancer, for the week ending 6 June 2014.

ChristmasMorning

Just some of the goodies at the American Society for Clinical Oncology conference 2014

It was a bit like Christmas morning unwrapping the presents that was the American Society for Clinical Oncology’s conference that was held 2 weeks’ ago.  It’s made for an extra-long Best of Breast (which is also a week late – sorry!).

There was fantastic new research into treatment-resistant breast cancer, HER-2 positive breast cancer and TNBC; however, what stands out is the first step to developing an immunotherapy approach to breast cancer by combining cryoablation and Ipilimumab (an immune stimulant that is already being used in melanomas).  Cryoablation breaks the tumour down and Ipilimumab allows the immune system to recognise the cancer cells.

The irony is that cryoablation is something I looked into shortly after my diagnosis, but I was told by my surgeon that it wouldn’t guarantee clean margins.  Well … what surgeons also don’t tell you is that clean margins will not guarantee the cancer won’t come back.  I’ve seen people who’ve had mastectomies who’ve had with recurrences (even with radiotherapy and chemotherapy to mop up) in the scar tissue.  So clean margins my foot.  There are no guarantees with surgery, chemotherapy or radiotherapy.  The medical establishment is conservative and playing a numbers game and it’s us patients who are being kept in the dark.

I think one of the drawbacks of doing Best of Breast is that I read about all these wonderful new developments and all I can think is:  why didn’t they come up with this 2 years’ ago, or why didn’t I do this 2 years ago?  Why are my clinicians stuck in the dark ages?  And I think of all my friends who’ve passed on, and I hope that a cure comes soon for all of us with cancer.

To cheer myself up, the lead article is about the blind mole rat.  I’d posted previously about the naked mole rat which is cancer-resistant, now there’s the blind mole rat (not related!) which has the same superhuman anti-cancer properties.  Scientists have decoded its genes and discovered the secret of how it never gets cancer.  The next step is to work out how to turn us all into blind mole rats … .

BlindMoleRat

See how they run … (The furry-but-blind blind mole rat (Spalax) is a close cousin to the common house mouse.) Image credit: bbc

1.  Cancer-resistant blind mole rat gets genome sequence

http://www.bbc.co.uk/news/science-environment-27684001

  • Scientists have sequenced the genome of the blind mole rat, a mammal that digs with its teeth, has skin over its eyes and lives for more than 20 years.
  • The rat”s underground lifestyle means coping with no light, very little oxygen and an awful lot of dirt.
  • It is also resistant to cancer.
  • One of the study’s lead authors, Prof Eviatar Nevo from the University of Haifa in Israel, has studied blind mole rats for more than 50 years.
  • In all of that time, a spontaneous tumour has never been discovered.
  • Even when treated with carcinogenic chemicals, these remarkable rodents were incredibly resistant to cancer.
  • Most animals rely on cells detecting a cancerous malfunction and shutting themselves down (programmed cell death or “apoptosis”), but the blind mole rat’s immune system attacks tumours and causes “necrosis” instead.
  • All this may have happened because one of the key mediators of the normal cell-shutdown defence, a protein called p53, is mutated in the mole rats as part of their adaptation to low oxygen.
  • The mole rat spends its entire life under the ground, where oxygen is scarce. In other animals this would send p53 into overdrive.
  • “When there is low oxygen, in other species, [normal p53] would mean that some cells would die from apoptosis – but not in blind mole rats, because that would be a disaster,” said Dr Denis Larkin from the Royal Veterinary College in London, one of the study’s authors.
  • So the mole rats have evolved a unique trade-off, weakening p53 and boosting the immune system’s necrotic defence, which the cancer doesn’t know how to deal with.
  • “When you have the whole genome… you can more efficiently use the species as a model – for cancer resistance, or adaptation to hypoxia, or other medical challenges.”

For more information:  Nature Communications 5, Article number:  3966  doi: 10.1038/ ncomms4966, Genome-wide adaptive complexes to underground stresses in blind mole rats Spalax

2.  Cryoablation and ipilimumab:  First immunotherapy treatment for breast cancer shows promise

http://www.mskcc.org/blog/new-immunotherapy-approach-breast-shows-promise

  • A new form of immunotherapy treatment — the first of its kind for breast cancer — is showing promising results in early research.
  • The treatment combines a technique called cryoablation, or freezing of the tumor, with an immunotherapy drug that has already proved effective in advanced melanoma, an aggressive form of skin cancer.
  • Ipilimumab works by blocking a protein called CTLA-4, which normally puts the brakes on the immune system. If the brakes are turned off, the immune system is able to mount a robust response and ideally destroy tumor cells.
  • The treatment is based on that idea that a tumor mass is difficult for the immune system to infiltrate and digest. But if you break the tumor mass down into tiny fragments, the immune system will have an easier time processing it.
  • In this technique, investigators from Memorial Sloan-Kettering used cryoablation to break the tumor into smaller pieces. Using MRI for guidance, a small needle is inserted into the tumor to create an ice ball, which freezes it and breaks it into tiny fragments.
  • The patients are also given a single dose of ipilimumab.
  • The intent of the treatment is to enable the immune system to recognize breast cancer fragments, remember that information, and consequently seek out and destroy any tumor cells that may appear in the body if the cancer recurs months or even years after surgery.

For more information:  ASCO, A pilot study of preoperative (Pre-op), single-dose ipilimumab (Ipi) and/or cryoablation (Cryo) in women (pts) with early-stage/resectable breast cancer (ESBC).

Popeye

I only eats the natural stuff, never synthetic spinach!

3.  Eating synthetic folate boosts cancer risk

  • Eating foods fortified with synthetic folate (vitamin B9) may increase risk of breast cancer in European American women, a study in the International Journal of Cancer suggests.
  • Although high intake of synthetic folate was linked to elevated risk of breast cancer, high intake of folate from natural foods was associated with 43% and 42% reduced risk of breast cancer and ER-positive tumors, respectively, in Black American women.
  • The study suggests that fortification of folate in wheat flour and processed foods may boost the risk of breast cancer in European American women, if not all women.
  • Synthetic folate is present not only in wheat flour and processed foods, but also used in many folate supplements.
  • Natural folate is found high in plant-based foods including beans, lentils, spinach, asparagus, lettuce, avocado, broccoli, and oranges.
  • No evidence suggests that high intake of natural folate causes any harm.

For more information: International Journal of Cancer, Volume 134, Issue 6, pages 1422-1435, 15 March 2014, Associations of dietary folate, Vitamins B6 and B12 and methionine intake with risk of breast cancer among African American and European American women

4.  Vitamin C or ascorbic acid has been known to protect against a variety of cancer.

  • A review in European Journal of Cancer provides evidence to suggest that taking vitamin C post-diagnosis can also significantly extend survival in breast cancer patients.
  • The review based on 10 articles of 17,696 breast cancer cases published in the PubMed database up to Feb 2014 shows that using vitamin C supplements was associated with 19% reduced risk of total mortality and 15% reduced risk of death from breast cancer.
  • Specifically, an additional 100-mg-per-day increase was associated with 27% reduced risk of death from all causes and 22% reduced risk of death from breast cancer.

Dietary vitamin C was also associated with significantly reduced risk of death from all causes and risk of death from breast cancer.

For more information:  Eur J Cancer. 2014 May;50(7):1223-31, Vitamin C and survival among women with breast cancer: a meta-analysis

5.  Four new genes discovered that increase inherited breast cancer risk

http://medicalxpress.com/news/2014-06-genes-familial-breast-cancer.html

  • RINT1, a gene, was previously not considered a human cancer susceptibility gene.
  • A study discovered there was a two- to three-fold increase in risk for breast cancer in families that carry a mutation in that gene.
  • RINT1 was also found to increase risk for a broad spectrum of gastrointestinal and gynecological cancers in these families.
  • In another study mutations in three other genes—MRE11A, RAD50, and NBN—were also confirmed to increase breast cancer risk.
  • The proteins encoded by these three genes form a tight complex that is involved in DNA repair, and the three genes had been considered likely candidates.

For more information:   Cancer Discovery Research, May 2, 2014; doi: 10.1158/2159-8290.CD-14-0212, Rare Mutations in RINT1Predispose Carriers to Breast and Lynch Syndrome-Spectrum Cancers

6.  Exposure to solvents prior to first childbirth ‘linked to breast cancer risk’

http://www.medicalnewstoday.com/articles/277576.php

  • In a study published in Cancer Research, women with a family history of breast cancer who worked with organic solvents prior to having their first child had an increased risk for hormone receptor-positive breast cancer.
  • Overall, they found no increased risk for breast cancer from exposure to solvents across the participants’ lifetimes.
  • A “nonsignificant elevated risk” was observed in women who worked as maids or housekeeping cleaners and those who had jobs in factories.
  • In 2004, a study published in the Proceedings of the National Academy of Sciences identified an industrial solvent that may put women at increased risk of breast cancers, miscarriages and irregular ovulation.
  • And in a 2013 study, researchers from the Danish Cancer Society Research Center in Denmark found an association between exposure to trichloroethylene – a widely-used chlorinated dry-cleaning solvent and degreaser – and increased risks of liver cancer and cervical cancer.

For more information:  American Association for Cancer Research, 30 May 2014, Exposure to Organic Solvents Before First Childbirth May Increase Hormone-related Breast Cancer Risk

7.  Breast cancer gene now linked to lung cancer among smokers

http://www.independent.co.uk/news/science/breast-cancer-gene-now-linked-to-lung-cancer-among-smokers-9468101.html

  • A gene linked to breast cancer has now been found to increase the chances of someone developing lung cancer, especially if they smoke, a study has found.
  • Mutations in the BRCA-2 gene are known to increase the risk of breast and ovarian cancers but for the first time scientists have shown that defects in the same gene significantly raise the probability of developing lung cancer.
  • If smokers carry BRCA-2 mutations then their lung cancer risk increases from 15 per cent – the risk that smokers already face – to 25 per cent over the course of their lifetime, the medical researchers found.

For more information:  Nature Genetics (2014) doi:10.1038/ng.3002, Rare variants of large effect in BRCA2 and CHEK2affect risk of lung cancer

8.  Skin cancer drug ‘cures’ man given months to live

http://www.dailymail.co.uk/health/article-2646773/Skin-cancer-drug-cures-man-given-months-live-Doctors-hail-results-astonishing-medical-trial-hope-millions.html

  • ‘Immunotherapy’ drug pembrolizumab lets immune system attack the disease
  • Doctors say medical trials show ‘jaw-dropping’ results for cancer patients
  • One man, Warwick Steele, 64, apparently ‘cured’ from skin cancer after taking drug for six months

9.  New leukaemia drug Ibrutinib boosts survival rate to 90% and may eventually replace chemotherapy and radiotherapy

http://www.dailymail.co.uk/health/article-2647973/Could-end-chemotherapy-New-leukemia-drug-boosts-survival-rate-90-eventually-replace-invasive-chemical-treatment.html

  • A breakthrough international trial of a new cancer drug has given researchers renewed hope in the fight against leukaemia, with one doctor suggesting it could end traditional chemotherapy treatments for good.
  • The results of a trial on 391 patients showed the drug Ibrutinib gave patients fighting a type of slow growing blood cancer called Chronic lymphocytic leukaemia (CLL) a 90 per cent chance of survival, eight higher than the 81 per cent who survive on chemotherapy treatment.
  • Patients on the trial responded quicker to the drug than chemotherapy and showed fewer side effects. What was also particularly encouraging was that patients who do not respond to, or have a resistance to chemotherapy treatments, now have an alternative.
  • The study was presented at ASCO 2014.

For more information: http://www.petermac.org/sites/default/files/Media%20release_Blockbuster%20worldwide%20clinical%20trial%20benefits%20people%20with%20advanced%20leukaemia_Jun2014.pdf

10.  Using Zoladex (Goserelin) to “rest” ovaries may prevent early menopause from chemotherapy

http://medicalxpress.com/news/2014-05-drug-treatment-early-menopause-breast.html

  • One of the most distressing side-effects of chemotherapy is early menopause.
  • Chemotherapy-induced menopause tends to come on suddenly, and consequently, symptoms are much more intense.
  • These symptoms include irregular periods and then cessation of periods completely; vaginal dryness; hot flashes; night sweats; sleep problems; mood changes; weight gain; thinning hair; dry skin; and loss of breast fullness.
  • However, the risk of early menopause can be significantly reduced by adding a drug called goserelin (Zoladex) to the chemotherapy regimen.
  • Also, women who took goserelin and wanted to have children were more likely to get pregnant and deliver a healthy baby.
  • The overall purpose of goserelin is to temporarily put the ovaries “at rest” during chemotherapy.
  • “We found that, in addition to reducing the risk of early menopause, and all of the symptoms that go along with menopause, goserelin was very safe and may even improve survival … these findings are going to change our clinical practice.”

For more information:  ASCO Daily News, 2 June 2014, Improved Fertility Preservation with Goserelin Added to Standard Chemotherapy for Patients with ER- Breast Cancer

Also: http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Hormonaltherapies/Individualhormonaltherapies/GoserelinBreast.aspx

studynewtest

Metastasis requires the presence of three cells in direct contact on a blood vessel wall: a tumor cell that produces the protein MENA; a peri-vascular macrophage (cells that guide tumor cells to blood vessels); and a blood-vessel endothelial cell. The presence of three such cells in contact with each other is called a tumor microenvironment of metastasis, or TMEM, which is depicted within the box in this illustration. Credit: Albert Einstein College of Medicine

11.  New test predicts if breast cancer will spread with greater accuracy

http://medicalxpress.com/news/2014-06-breast-cancer_1.html

  • A new test has been developed that is more accurate in predicting the risk of distant tumor spread than a test closely resembling the leading breast cancer prognostic indicator on the market.
  • Currently-marketed tests assess risk for breast cancer metastasis by looking for changes in gene expression or in levels of proteins associated with growth of tumor cells.
  • But those changes don’t reflect the mechanism by which individual tumor cells invade blood vessels, a necessary step for metastasis.
  • By contrast, this new test is based on what researchers learned from intravital imaging, which reveals biological processes deep within the tissues of a living animal.
  • Using this technology, they determined how breast cancer tumor cells spread in rodents.
  • Observations showed that primary breast cancers metastasize when a specific trio of cells is present together in the same microanatomic site: an endothelial cell (a type of cell that lines the blood vessels), a perivascular macrophage (a type of immune cell found near blood vessels) and a tumor cell that produces high levels of Mena, a protein that enhances a cancer cell’s ability to spread.
  • A site where these three cells touch is where tumor cells can enter blood vessels.
  • That site is called a tumor microenvironment of metastasis, or TMEM (see accompanying figure).
  • A strong and statistically significant association was found between TMEM score and risk of metastasis in the most common type of breast cancer.
  • The study was led by researchers at the National Cancer Institute (NCI)—designated Albert Einstein Cancer Center of Albert Einstein College of Medicine of Yeshiva University and Montefiore Einstein Center for Cancer Care.

For more information:  Journal of the National Cancer Institute  (2014)  106  (8):  dju136doi: 10.1093/jnci/dj, Tumor Microenvironment of Metastasis and Risk of Distant Metastasis of Breast Cancer

12.  Drinking tea may reduce risk of breast cancer

http://www.femalefirst.co.uk/health/tea-drinkers-reduced-risk-of-breast-cancer-479895.html

  • Tea drinkers could have less of a breast cancer risk, according to a new study.
  • Thirty-nine studies involving 13,204 breast cancer cases and 87,248 controls were identified for the meta-analysis.
  • The aim of this latest analysis was to evaluate the links between tea consumption and alcohol drinking and physical activity and breast cancer risk among Chinese women.
  • “Compared with non-drinkers, regular tea drinkers had a 21 per cent decreased risk of breast cancer.
  • This beneficial finding is likely to be associated with the polyphenol content of tea.
  • Tea is rich in polyphenols, including catechins and gallocatchins, which have been reported to have antioxidant activity and potential anti-tumour effect.

13.  New way to treat HER2-positive treatment-resistant breast cancer

http://www.oncologynurseadvisor.com/powerful-new-way-to-treat-her2-positive-breast-cancer-validated/article/349950/

  • Although HER2-positive breast cancer can be treated with the drug Herceptin, it typically develops resistance within several years.
  • A multi-institutional team has found a means of inhibiting another protein, protein tyrosine phosphatase 1B (PTP1B), whose expression is also upregulated in HER2-positive breast cancer.
  • PTP1B has a critical role in the development of tumors in which HER2 signaling is aberrant.

For more information:  Nature Chemical Biology (2014) doi:10.1038/nchembio.1528,  Targeting the disordered C terminus of PTP1B with an allosteric inhibitor

14.  Insulin-resistant Metastatic Breast Cancer Patients Fare Worse

http://www.cancernetwork.com/asco-2014-breast-cancer/insulin-resistant-metastatic-breast-cancer-patients-fare-worse

  • Women with breast cancer who have type 2 diabetes or glucose intolerance has been linked to a poorer overall survival. Still, the association between insulin levels, diabetes, and metastatic breast cancer is not clear.
  • “Insulin resistance is associated with a pro-inflammatory state that may be responsible for treatment failure.  We must also consider that tissue insulin sensitivity may be different from overall insulin sensitivity, which is assessed by the HOMA index, and that breast cancer tissues may also have different insulin sensitivity.”

For more information:  ASCO:  Impact of insulin resistance (IR) on the prognosis of metastatic breast cancer (MBC) patients treated with first-line chemotherapy (CT)

15.  Vitamin D levels not tied to breast cancer outcomes

http://www.medpagetoday.com/HematologyOncology/BreastCancer/46116

  • In a sub-study of a large randomized trial, levels of 25-hydroxyvitamin D (25(OH)D) were not associated with overall survival (OS), relapse-free survival, or breast cancer-specific mortality, according to Ana Elisa Lohmann, MD, of Mount Sinai Hospital in Toronto, and colleagues.
  • The findings don’t support the notion of vitamin D supplements as a way to improve outcomes, Lohmann said at theAmerican Society of Clinical Oncology annual meeting.
  • She cautioned that the study was a post-hoc analysis of a subset of patients who were not fully representative of the whole trial population and vitamin D was only measured once.
  • She also noted that the researchers had no information about vitamin D supplementation, which recent studies have shown is common.

For more information:  American Society of Clinical Oncology, “Prognostic associations of 25OH vitamin D in NCIC CTG MA.21, a phase III adjuvant RCT of three chemotherapy regimens (EC/T, CEF, AC/T) in high-risk breast cancer (BC)” ASCO 2014; Abstract 504

16.  Some breast cancer patients may get drug-linked heart failure but don’t seek treatment

http://health.usnews.com/health-news/articles/2014/06/03/some-breast-cancer-patients-may-get-drug-linked-heart-failure-study

  • More than one in 10 older breast cancer patients treated with certain chemotherapy drugs develop heart failure, but many don’t get proper treatment for their heart condition, a new study suggests.
  • However, the majority of older women who develop heart problems after their breast cancer therapy aren’t treated by a cardiologist, and they had lower quality of care
  • The researchers analysed Medicare data on 8,400 breast cancer patients older than 65 who were treated either with chemotherapy drugs called anthracyclines, or a targeted therapy called trastuzumab. Prior research has linked both of these treatments to heart problems.
  • About 12 percent of the patients did develop heart failure within three years after their cancer treatment, but only one-third of them saw a cardiologist within 90 days of developing the symptoms, the study found.
  • The study is to be presented at an American Heart Association meeting in Baltimore.

17.  Veliparib (ABT-888) effective in treating patients with cancers related to the BRCA 1 or 2 genetic mutations

  • Veliparib (ABT-888), is a PARP inhibitor, which means it lowers the resistance of cancer cells to treatment by targeting the polymerase (PARP) family of enzymes responsible for a wide variety of cellular processes in cancer cells, particularly DNA repair.
  • “Cancer cells have increased levels of PARP, which we believe may, in part, lead to resistance to chemotherapies and other cancer treatments.
  • “Tumor cells in patients with BRCA mutations are particularly sensitive to the effects of PARP inhibitors due to underlying DNA repair abnormalities caused by the BRCA mutation.
  • Veliparib can act as personalized medicine for patients with tumors caused by an inherited BRCA mutation, due to this particular sensitivity.”

For more information:   A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation. SGO Annual Meeting. Abstract 136. Presented March 25, 2014.

18.  Oncotype DX DCIS Score Changes Treatment Recommendations for One Out of Three Patients with Pre-Invasive Breast Cancer

http://www.marketwatch.com/story/multiple-studies-presented-at-asco-annual-meeting-demonstrate-unique-practice-changing-impact-of-oncotype-dx-to-optimize-cancer-care-2014-06-01?reflink=MW_news_stmp

  • Ductal carcinoma in situ (DCIS), also referred to as stage 0 breast cancer, affects one out of every five women diagnosed with breast cancer in the United States and is often treated with surgery followed by radiation therapy and/or hormonal therapy.
  • With only 20 percent of cases estimated to recur or turn into invasive breast cancer, it is estimated that about 40,000 women each year receive additional treatments that may not be needed.
  • “Currently, most DCIS patients are treated with surgery followed by radiation, despite the fact that no treatment beyond surgery has been shown to impact long-term survival,” said Michael Alvarado, M.D., associate professor of surgery, the University of California, San Francisco (UCSF).
  • “These results highlight the huge need in optimizing treatment of this non-invasive, indolent form of breast disease, and the importance of the Oncotype DX DCIS Score to help physicians reduce over- and under-treatment of DCIS.”

19.  New research shows potential targeted therapy for metastatic, androgen receptor positive, breast cancer

http://www.healthcanal.com/cancers/breast-cancer/51442-new-research-shows-potential-targeted-therapy-for-metastatic-androgen-receptor-positive-breast-cancer.html

  • Enobosarm is an oral, nonsteroidal selective androgen receptor modulator (SARM) that has been developed for its selective androgenic activity with minimal side effects (i.e. no masculinisation or muscle aches or nausea) as it is tissue-specific.
  • More than 80% of estrogen receptor positive metastatic breast cancer is androgen receptor positive, supporting the development of targeted therapy for the androgen receptor in this patient population.
  • Results from an open label clinical study, evaluating an oral daily dose of the drug enobosarm, shows promise for women with metastatic, androgen receptor positive, estrogen receptor positive breast cancer.
  • The new data is from a phase 2 study to be reported on Monday, June 2, 2014 at the meeting in Chicago of the American Society of Clinical Oncology (ASCO) by Beth Overmoyer, MD, director of the Inflammatory Breast Cancer Program at the Susan F. Smith Center for Women’s Cancersat Dana-Farber Cancer Institute.

20.  Women with metastatic breast cancer can safely receive bisphosphonates less frequently

http://esciencenews.com/articles/2014/06/02/women.with.metastatic.breast.cancer.can.safely.receive.bisphosphonates.less.frequently.without.comp

  • Women with metastatic breast cancer to the bone may be able to receive bisphosphonates, the bone-targeting class of drugs like zoledronic acid, less often after the first year of monthly administration.
  • Like all bisphosphonates, zoledronic acid has some safety concerns:  Osteonecrosis of the jaw, long-bone fractures, and chronic kidney function impairment are 3 adverse events of “special interest.”
  • Less-frequent dosing of zoledronic acid, compared with the standard monthly dosing, was associated with fewer cases of osteonecrosis of the jaw (2 vs 0) and lower rates of chronic kidney function impairment (7.9% vs 9.6%).
  • There were no cases of long-bone fractures (i.e., atypical femoral fractures). However, these findings were not statistically significant.
  • Clinicians give zoledronic acid 4 mg as an intravenous (IV) infusion every 3 to 4 weeks for the first year after the diagnosis of bone metastases. This is standard dosing, approved by the US Food and Drug Administration.
  • However, in the randomized trial known as OPTIMIZE-2, a less-intense schedule of zoledronic acid — administered every 12 weeks — was found to be comparable in efficacy to once-a-month schedule after 1 year of the standard schedule.
  • With that practice change, women may also reduce their risk of serious side effects.

For more information:  2014 Annual Meeting of the American Society of Clinical Oncology (ASCO).Abstract LBA9500, Efficacy and safety of continued zoledronic acid every 4 weeks versus every 12 weeks in women with bone metastases from breast cancer: Results of the OPTIMIZE-2 trial.

21.  Combination therapy shows promise against triple-negative breast cancer

http://www.healthcanal.com/cancers/ovarian-cancer/51444-combination-therapy-shows-promise-against-forms-of-breast-and-ovarian-cancer-in-early-clinical-trial.html

  • A two-drug combination that disrupts critical signaling circuits in cancer cells has produced an observable benefit in patients with recurrent high-grade serous ovarian cancer (HGSC) or triple-negative breast cancer (TNBC).
  • The study, which tested successively higher doses of the targeted drugs BKM120 and olaparib in 46 patients, focused on the safety of the treatment, the optimal dosage, how the drugs are metabolized, and their anti-cancer activity.
  • At each dose level tested, there was evidence of clinical benefit – tumors either shrank or stopped expanding.
  • Side effects were similar to those associated with BKM120 or olaparib alone.
  • BKM120, which inhibits the PI3K signaling pathway in cells, and olaparib, which blocks the PARP-1 protein, had previously been shown to enhance each other’s effectiveness in mice with TNBC or with breast cancer linked to mutations in the BRCA1 gene (triple-negative breast tumors lack estrogen and progesterone receptors as well as the human epidermal growth factor receptor 2).
  • Other studies had found olaparib to be active in HGSC and in ovarian and breast cancers linked to inherited BRCA mutations.  These and other findings led researchers to test the drugs in tandem in patients with recurrent HGSC or TNBC.
  • For more information:  http://www.dana-farber.org/Newsroom/News-Releases/combination-therapy-shows-promise-against-forms-of-breast-and-ovarian-cancer-in-early-clinical-trial.aspx and ASCO:  Phase I study of oral BKM120 and oral olaparib for high-grade serous ovarian cancer (HGSC) or triple-negative breast cancer (TNBC).

22.  New way to predict response to chemotherapy in triple-negative breast cancer

  • The presence of tumor-infiltrating lymphocytes ahead of treatment may help predict response to platinum-based chemotherapy in women with triple-negative breast cancer, according to a new study.
  • Response to platinum-based neoadjuvant chemotherapy was found to be predicted by tumor-infiltrating lymphocytes found in the connective tissue and the tumor itself.
  • Tumor-infiltrating lymphocytes were significantly associated with subtypes of triple-negative breast cancer.
  • The highest frequency of tumor-infiltrating lymphocytes occurred in the immunomodulatory subtype of triple-negative breast cancer.
  • The data is being presented at the American Society for Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

For more information:  Association of increased tumor-infiltrating lymphocytes (TILs) with immunomodulatory (IM) triple-negative breast cancer (TNBC) subtype and response to neoadjuvant platinum-based therapy in PrECOG0105.

23.  Some HER2-positive early-stage breast cancer patients may not benefit from more aggressive chemotherapy treatments

http://www.cancernetwork.com/asco-2014-breast-cancer/dual-her2-targeting-benefits-subset-breast-cancer-patients

  • A follow-up analysis of gene expression signatures from the Cancer and Leukemia Group B (CALGB) 40601 neoadjuvant phase III clinical trial shows that certain HER2-positive early-stage breast cancer patients may not benefit from more aggressive chemotherapy treatments as part of a neoadjuvant regimen.
  • The study further confirms that HER2-positive breast cancer is a molecularly disparate disease, not unlike triple-negative disease.
  • The efficacy results from the trial, presented at the 2013 meeting, showed that combining two HER2-targeted agents—trastuzumab and lapatinib—in the neoadjuvant setting was not more effective in yielding pathologic complete responses (pCRs), as compared with trastuzumab alone.
  • The motivation for this analysis was the increasing recognition that even clinical subtypes of breast cancer have substantial variability in biology, which may dictate response to therapy, and particularly, that response to chemotherapy can vary depending on the subtype of disease.
  • Additionally, patients who had a pCR were more likely to have a high expression of immune signatures, although the exact role of specific immune responses is not clear.

24.  Alterations in LRIG1 Gene May Increase the Risk for Breast Cancer Relapse and Death

http://www.healthcanal.com/cancers/breast-cancer/51439-alterations-in-lrig1-gene-may-increase-the-risk-for-breast-cancer-relapse-and-death.html

  • Tumors with metastatic capability have cells within them that have stem cell-like properties, which resist chemotherapy, tend to sit quietly in the tumor, and are most likely the source of metastatic spread.
  • LRIG1 is a protein that is thought to control the growth of these cells and keep them quiet.
  • Human cells have two copies of most genes. An increase or decrease in copy-number of certain genes is implicated in several diseases, including cancer.
  • “First, we found that the loss of LRIG1 gene copy-numbers in tumors of early-stage patients was associated with a higher risk of disease relapse, metastasis, and death.”
  • “Second, we observed that the patients whose tumors had an increase in the copy-numbers of LRIG1 had much better clinical and pathology characteristics, generally. This suggested that the gain of LRIG1 copy-numbers may contribute to the lower risk observed in these patients.”

For more information:  The Journal of Cancer Research, June 1, 2014 74:29282935doi:10.1158/0008-5472.CAN-13-2112, Loss of LRIG1 Locus Increases Risk of Early and Late Relapse of Stage I/II Breast Cancer

25.  Halting hnRNPM protein in cancer cells may restrict metastasis

  • Working with human breast cancer cells and mouse models of breast cancer, scientists identified a new protein, hnRNPM, that plays a key role in reprogramming cancer cells to migrate and invade other organs.
  • When that protein is removed from cancer cells in mice, the ability of the cells to metastasize to the lung is dramatically decreased.
  • The protein, hnRNPM, helps launch a cascade of events that enables breast cancer cells to break away from the original tumor, penetrate the blood stream, invade another part of the body and form a new nodule of that tumor.
  • Scientists found aggressive breast tumors, including those that show metastatic traits, expressed higher levels of hnRNPM.
  • “This confirmed hnRNPM’s role in the metastasis of human breast cancer.  Now we’re investigating how the protein works in order to be able to develop a drug that could prevent tumor metastasis.”

For more information:  Genes and Development Journal,  June 1, 2014 vol. 28 no. 111191-1203, Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing

26.  Myriad Genetics Inc.  Presents Data on BRACAnalysis CDx and HRD in predicting response for triple-negative breast cancer

http://online.wsj.com/article/PR-CO-20140530-906110.html

  • Myriad Genetics, Inc., a global leader in molecular diagnostics, announced the presentation of new data at the American Society of Clinical Oncology (ASCO) meeting this week that supports the clinical efficacy of its BRACAnalysis CDx(TM) and HRD(TM) tests in predicting platinum-based therapy response for breast cancer patients.
  • Myriad also will present data looking at the ability of the Company’s proprietary HRD tumor test in terms of its ability to predict response among triple negative breast cancer patients.
  • In addition, Myriad announced a new 160 patient randomized study evaluating HRD as a biomarker for prediction of cisplatin and paclitaxel response in triple negative breast cancer patients at diagnosis.
  • “High HRD scores have been shown in early research to be highly correlated with response rates to DNA damaging agents such as platinum based therapies,” said Jerry Lanchbury, chief scientific officer at Myriad Genetics.
  • “We believe that, with further validation, the HRD test has the potential to become the gold standard diagnostic to identify patients who have lost DNA repair function and are most suitable for this class of therapeutics.”

27.  Higher Breast Cancer Risk for Childhood Cancer Survivors

  • Women who survived a childhood cancer were at elevated risk for breast cancer even if they were never exposed to chest radiation during their initial therapy, a researcher said here.
  • These women had nearly four times the risk of the disease as women in the general population, according to Tara Henderson, MD, MPH, of the University of Chicago.
  • Also, they tended to get the disease at a much younger age and were also more likely to get bilateral breast cancer, Henderson said at the American Society of Clinical Oncology annual meeting.
  • The latter two characteristics were similar to what is seen among women who had been exposed to chest radiation, where the increased risk of later breast cancer has been well established.

For more information:  American Society of Clinical Oncology.  “Breast cancer in childhood cancer survivors not treated with chest-directed radiation in the Childhood Cancer Survivor Study (CCSS)”ASCO 2014; Abstract 10009.

28.  Targetting the progesterone receptor in new breast cancer treatments

  • Approximately two out of three breast cancers are driven by receptors that bind the hormones estrogen and progesterone—when the hormones bind to these receptors in cancer cells, they signal the cancer cells to grow.
  • What makes the progesterone receptor therapeutically interesting is that it has two activation domains—AF1 and AF2.
  • Normally, both are needed for full activation of the receptor.
  • The study pinpoints just how AF2 communicates with AF1—the first evidence of the long-range interaction between these two functional domains.  These findings support further research to look for promising small molecules that block that interaction.
  • The findings are especially important because in some mutations AF2 is deleted, yet the receptor still drives the cancer using its AF1 domain.
  • Current drugs used for treating these cancers only target the AF2 domain, so with nothing to bind to, they do not work at all.
  • While several studies have shown the importance of AF1, its binding domain is remarkably dynamic, frequently shifting shape and making it difficult to target with drugs.

For more information:  Structure, DOI: 10.1016/j.str.2014.04.013, Influence of Domain Interactions on Conformational Mobility of the Progesterone Receptor Detected by Hydrogen/Deuterium Exchange Mass Spectrometry

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