News for Breast Cancer and Cancer, from Google Alerts, for the week ending 7 November 2014.
[Apologies, I’m so behind in Best of Breast it’s no joke. I’ve been sorting out personal issues the past months which have taken priority. Looks as though I’ll be spending the festive season playing catch-up!]
One of the highlights this week is the proof that biphosphonates, used in breast cancer that has spread to the bones, can also prolong survival. But before you all go out and get the family pack, please note that one of the possible side-effects of biphosphonates is osteonecrosis of the jaw (localised death of bone tissue).
There’s also more evidence to show that mindfulness meditation can affect the body at the cellular level.
1. Biphosphonates can act on breast cancer tumours and prolong survival
- Biphosphonates are prescribed to people with osteoporosis and those with late-stage cancers that have spread to bone.
- In recent years there have been a number of trials suggesting these drugs prolong survival in women with breast cancer.
- However, researchers did not exactly know why.
- In the medical world, it has been assumed bisphosphonates would not get into tumours other than bone cancers at any concentration that could make a difference.
- Now a team from Sydney’s Garvan Institute of Medical Research has used imaging technology to show exactly how the drugs can target cells in tumours outside the skeleton, including breast cancer.
- “This study is potentially transformative for treatment of some cancers, because it is telling us for the first time that drugs we thought acted only in bone can also act within tumours completely outside the skeleton.
- Breast tumours often contain particles of calcium.
- Calcium phosphate – the predominant form of calcium seen in breast tissue – is frequently associated with malignancy.
- To see if bisphosphonates interact with breast calcium, the researchers attached to a chemical that glows under a microscope to the drug.
- They then gave the medication to mice with breast cancer and watched on a screen what happened.
- The imaging videos show how the bisphosphonates attach to tiny calcifications in tumours. The calcium and drug complexes are then devoured by tumour-associated macrophages – immune cells that the cancer hijacks early in its development to conceal its existence.
- After the macrophages have gobbled up these complexes they then switch sides and attack the cancer.
- “We do not yet fully understand how the macrophages revert from being bad cops to being good cops, although it is clear that this immune cell interacts with tumours, and probably changes its function in the presence of bisphosphonates.”
- Once the team realised what was happening in mice, they obtained a tumour sample from a patient with breast cancer who had undergone surgery.
- Tests on the tissue indicated the same process happens in humans.
For more information: Cancer Discovery, October 13, 2014; doi:10.1158/2159-8290.CD-14-0621, Real-Time Intravital Imaging Establishes Tumor-Associated Macrophages as the Extraskeletal Target of Bisphosphonate Action in Cancer
2. Could Japanese mushrooms kill the HPV virus that causes cervical cancer?
- Extract found in shiitake mushrooms may help prevent HPV-related cancers
- HPV is a contagious infection that affects skin, cervix, mouth and throat
- Shiitake mushrooms contain chemical AHCC which may boost immunity
- 5/10 women given extract were succesfully treated for cervical cancer
- Previous research shows AHCC can help block tumour growth
- In mice, AHCC led to the eradication of HPV within 90 days
For more information:11th International Conference of the Society for Integrative Oncology, Evaluation of Active Hexose Correlated Compound (AHCC) for the Eradication of HPV Infections in Women (138) presented by Judith Smith, PharmD
3. Dietary trial seeks breast cancer survivors
- A study at the University of Texas Health Science Center at San Antonio is looking at the protection provided by a diet that incorporates anti-inflammatory foods such as black tea, garlic, walnuts and green leafy vegetables.
- The study, Rx for Better Breast Health, involves about 150 women ages 18 to 75 who are overweight and breast cancer survivors.
- Half the women attend monthly lectures about anti-inflammatory foods and cancer, where a chef performs a Food Network-style cooking demonstration. The women receive recipes for tasty, healthful, easy-to-prepare dishes and follow-up counseling.
- The other group receives information about nutrition from the American Institute for Cancer Research.
- Anti-inflammatory foods include green and black tea, deep-water fatty fish (such as wild salmon), nuts, olive oil and colorful vegetables.
- Spices such as ginger, turmeric and black pepper can enhance the inflammation-reduction properties.
- To measure the effects of the diet, researchers are drawing the subjects’ blood and looking for a decrease in C-reactive protein.
- C-reactive protein measures whole-body inflammation. Research has found that breast cancer survivors with elevated levels of the marker have a higher risk of recurrence of the cancer; their risk of dying from cancer also is higher.
- To better understand the association between obesity and cancer, the researchers also are measuring something called circulating adipose stromal cells, which have been linked to increased risk for breast cancer recurrence. They’re more often found in women who are overweight.
- The study began in June 2014 and will wrap up in spring 2015. The recruitment is rolling, and openings are still available. Call 210-562-6579.
For more information: Rx for Better Health.
4. FAK molecule throws new insight into breast cancer recurrence and resistance to treatment
- Even with treatment up to one in five patients will see their DCIS come back, either as DCIS or as invasive breast cancer.
- Now researchers have investigated the role of a molecule known as FAK in controlling the resistance of DCIS to radiation and in predicting disease recurrence.
- “We know that cancer stem cells are able to avoid or repair damage caused by treatment. We wanted to look at how FAK is involved in this treatment resistance.”
- The team found that cancer cell samples containing more cancer stem cells had increased levels of FAK and that these samples were better able to survive radiotherapy.
- By examining patient tissue samples and information about whether each person had had a recurrence, the scientists discovered that high FAK activity was linked to the disease returning, either as DCIS or invasive breast cancer.
- In further work, a drug that blocks FAK reduced the formation of mammospheres, or clumps of breast cancer stem cells, showing FAK is important in cancer stem cell activity.
- By combining this inhibition of FAK with radiotherapy, the group was able to achieve a greater treatment effect than with either therapy alone.
- This knowledge could help doctors avoid over-treating those patients whose DCIS won’t come back, while making sure treatment is working for women who need it.
For more information: Stem Cells doi: 10.1002/stem.1843, Focal adhesion kinase and wnt signalling regulates human ductal carcinoma in situ stem cell activity and response to radiotherapy
5. Yoga and mindfulness practices found to assist breast cancer recovery at cellular level
- Breast cancer survivors who are involved in support groups, or who practice meditation and yoga, can make a positive physical impact at the cellular level when in recovery following treatment.
- The study found that telomeres, which are protein complexes at the end of chromosomes, maintain their length in breast cancer survivors who have psychological intervention, while telomeres shortened in women who were not involved in support groups.
- Shortened telomeres are associated with diseases, while longer ones are thought to help protect the body.
- While the study showed a short-term effect for breast cancer survivors, further research needs to be done to know if the effects are long lasting and if they apply to other cancers.
For more information: Cancer, DOI: 10.1002/cncr.29063, Mindfulness-based cancer recovery and supportive-expressive therapy maintain telomere length relative to controls in distressed breast cancer survivors
6. Women with Downs Syndrome have a lower incidence of breast cancer
- Breast cancer is one of the most common malignancies in women, but remarkably, that’s not true for women with Down syndrome.
- Recent studies show the extra chromosome that causes Down syndrome may also offer protection from breast cancer.
- “Overall there’s 96 percent fewer cases of breast cancer occurring in people with Down syndrome than the typical population.”
- In Denmark, researchers have been tracking all residents with Down syndrome since 1961. So far, they have seen zero cases of breast cancer.
7. ‘Battling’ cancer metaphors can make terminally ill patients worse
8. New insight into the causes of post-pregnancy breast cancer
- Nearly 25 percent of all breast cancers among premenopausal women occur within two to five years following a pregnancy.
- These postpartum tumors are more likely to spread or metastasize to other parts of the body, leading to an increased risk of death.
- Breast tissues undergo massive transformations during pregnancy in preparation for nursing the new infant. After milk production has ended, there is a cascade of cell death.
- “This cell death removes about 90 percent of breast epithelial cells during a very short window of time, which triggers widespread remodeling and repair of breast tissue by the immune system.”
- During this remodeling, immune cells called macrophages operate like tiny Pac-Man arcade game characters, gobbling up the dying cells before the dying cells can release intracellular contents which can provoke immune attack.
- As another safeguard against immune attack, macrophages that ‘eat’ dying cells also secrete immune suppressive factors. Macrophages use one molecule — MerTK — to control both of those processes.
- Using a mouse model, scientists found that immune suppression in the postpartum breast triggered by MerTK mistakenly protects tumors, increasing their ability to spread.
- “This is similar to an amplified wound healing response that is orchestrated and amplified by MerTK, and that drives tumor malignancy.”
- Results suggest that using a MerTK inhibitor in conjunction with other therapies could be helpful.
- In the meantime, women who have recently given birth need to be vigilant about breast health.
For more information: J Clin Invest. 2014;124(11):4737-4752. doi: 10.1172/JCI76375, Efferocytosis produces a prometastatic landscape during postpartum mammary gland involution
9. ‘Sea sponge’ drug may extend life for metastatic and triple-negative breast cancer patients
- Eribulin, originally developed from sea sponges, was also found to be the best treatment for those women suffering from an advanced triple negative form of breast cancer.
- The survival of the patient with an advanced form of the disease while taking the medicine could in some cases be extended for nearly five months.
- Eribulin, a “microtubule inhibitor” drug stops the cancer cells from separating into two new cells, thus slowing down the metastasis process, which is responsible for around 90 per cent of all cancer deaths.
- After metastasis takes root, a 10-year survival is around 1 in 10, compared to 9 in 10 for those diagnosed at the earliest stage.
For more information: National Cancer Research Institute (NCRI) Cancer Conference, Efficacy of eribulin in patients with metastatic breast cancer (MBC): a pooled analysis by HER2 and ER status
10. Rewiring cell metabolism slows colorectal cancer growth
- Many types of cancers (including brain, breast, and colon) have significantly less of a protein complex, called the mitochondrial pyruvate carrier (MPC), within them as compared to normal tissue.
- The amount of MPC within a patient’s tumor correlates with patient survival: the less MPC, the more aggressive the cancer.
- Re-introduction of MPC into cancer cells inhibits tumor growth, when cells are grown under conditions commonly used for assessing tumor initiation and metastasis, including after injection into mice.
- Known as the Warburg effect, changes in metabolism have long been known to be important for supporting uncontrolled growth in cancer. MPC, which operates at a critical branch point in carbohydrate metabolism, counteracts the Warburg effect.
- The role of MPC in the normal cell, and what loss of MPC does to a cancer cell, addresses an observation first made nearly one century ago. Nobel Prize-wining biochemist Otto Warburg noted that cancer cells change their metabolism to support uncontrolled growth and proliferation.
- Scientists later found the way in which the metabolite pyruvate is processed is key to these metabolic changes.
- In normal adult cells, pyruvate enters the mitochondria, the cell’s powerhouse, and fuels energy production.
- In cancer, pyruvate is diverted from the mitochondria to an alternative metabolic pathway that makes cell-building material.
- Scientists had long suspected the so-called Warburg effect seen in cancer was contingent upon controlling entry of pyruvate into the mitochondria. But there was no way to directly test the idea until two years ago, when Rutter’s group and others identified MPC as pyruvate’s doorway to the mitochondria.
- The current report in Molecular Cell shows that cancer cells shut that door by repressing MPC, and that experimentally re-opening the door by re-introducing MPC not only inhibits cancer growth, but also redirects pyruvate to the metabolic pathway used in normal cells. In other words, MPC counteracts the Warburg effect.
- The finding opens new opportunities for developing cancer therapeutics.
For more information: Molecular Cell, Volume 56, Issue 3, p400–413, 6 November 2014, “A Role for the Mitochondrial Pyruvate Carrier as a Repressor of the Warburg Effect and Colon Cancer Growth”
11. For patients with schizophrenia and breast cancer, adjuvant radiation therapy may not be preferable
- Researchers have found that for patients with schizophrenia and breast cancer, initial radical surgery without adjuvant radiation therapy may be preferred.
- For the study, researchers sought to investigate how patients with schizophrenia who later develop breast cancer handle treatment with adjuvant radiation.
- The findings suggest that patients with both schizophrenia and breast cancer do not fully comprehend their diseases.
- In addition, patients with schizophrenia are often non-compliant with recommended standard therapies, especially those that depend upon adjuvant radiation therapy.
- Therefore, the research suggest that strategies that involve conserving the breast may not be the best option, and initial radical surgery without the use of radiation may be better for the patient.
- For more information: The American Journal of Surgery, Adjuvant radiation therapy for breast cancer in patients with schizophrenia
12. ‘Invisible tattoos’ could improve body confidence after breast cancer radiotherapy
- Invisible tattoos could replace the permanent dark ink tattoos used to ensure that breast cancer patients having radiotherapy are treated in exactly the same spot during each session.
- Research suggests that the permanent pin prick marks made on the skin of women having radiotherapy reminds them of their diagnosis for years to come, reducing body confidence and self-esteem.
- It’s also more difficult to spot these tattoos in dark-skinned women, potentially leading to inconsistencies in the area being treated.
- The researchers found that 56 per cent of the women who had fluorescent tattoos felt better about their bodies one month after treatment, compared to only 14 per cent among those who received black ink tattoos.
- For more information: 2014 NCRI Cancer Conference, Breast Radiotherapy: Invisible Tattoos for External References
13. New guidelines on surgical margins and radiotherapy should be considered
- Recent research and guidelines have changed how surgeons should be thinking about some aspects of treating breast cancer, a panel of experts said in a press briefing at the annual clinical congress of the American College of Surgeons.
- New guidelines on surgical margins, data supporting radiation rather than complete lymphadenectomy for patients with positive sentinel nodes, and other studies supporting targeted radiation therapy instead of whole-breast irradiation after lumpectomy should be on a surgeons’s radar.
- The 2014 joint guidelines from the Society of Surgical Oncology and the American Society of Radiation Oncology based the recommendations on a meta-analysis of studies that found no advantage to wider excision margins for preventing in-breast recurrence (Ann. Surg. Oncol. 2014;21:717-730).
- The guidelines apply only to patients with invasive cancer undergoing breast-conserving treatment, he noted. There are no guidelines yet specifically for surgical margins in women undergoing mastectomy for breast cancer, nor for women with ductal carcinoma in situ (DCIS).
- While there is no evidence that a margin width wider than “no ink on tumor” is better for women undergoing mastectomy, the guidelines should not be extrapolated to women having mastectomies “because they will generally not undergo adjuvant radiation therapy.”
- A separate recent study should change the way surgeons approach decisions about axillary surgery in patients with breast cancer.
- A study was conducted that randomized women who had cancer in sentinel lymph nodes after mastectomy to further treatment by removing the rest of the lymph nodes under the arm, as is common practice, or to radiation of the lymph nodes area.
- Rates of cancer recurrence did not differ between groups but the radiation approach significantly reduced the risk of lymphedema and other morbidity
- Also on the topic of radiation therapy, two recent studies of targeted breast irradiation rather than whole-breast radiotherapy suggest that the targeted approach may be beneficial.
- Whole-breast radiation after lumpectomy reduces the risk of local recurrence by 50%, previous studies have shown, but it comes with potential side effects including burns, lymphedema, and damage to underlying structures like the heart and lungs. Patients who don’t live near specialized radiation centers may not be able to access the daily month-long treatments.
- Overall survival and breast cancer survival were similar in the intraoperative and whole-breast radiation groups except for worse outcomes in patients who had intraoperative radiation done as a second surgery after the operation to perform lumpectomy.
- The rate of deaths from causes other than breast cancer was higher in the whole-breast radiation group, in many cases due to cardiac events.
- Whole-breast radiation on the left side of the chest has been shown to accelerate atherosclerosis of the vessels in the heart, and it may be that avoiding this through intraoperative targeted radiotherapy may provide a cardiovascular benefit, though this is yet to be proven.