Assessment of Molecular Relapse Detection in Early-Stage Breast Cancer

• This prospective, multicenter, sample collection study assessed the clinical validity of molecular relapse detection with circulating tumor DNA (ctDNA) in early-stage breast cancer. The primary endpoint was relapse-free survival. Detection of ctDNA during follow-up was associated with relapse (HR, 25.5; P<.001). Detection of ctDNA at diagnosis, prior to any treatment, was also associated with shorter relapse-free survival (HR, 5.8; P=.01). Detection of ctDNA had a median lead time of 10.7 months compared with clinical relapse and performed better in distant extracranial metastatic relapse (detected in 96%) versus brain-only metastasis (17%).

• These important findings suggest the potential for ctDNA in follow-up of early-stage breast cancer. Further studies to assess the potential for this information to guide adjuvant therapy are needed.
• Meaning The findings suggest that molecular relapse detection has high levels of clinical validity, and clinical trials of treatment initiated at molecular relapse without waiting for incurable metastatic disease to develop are needed.

aterry: Based on the discussion in the referenced articles and other things I have read, I believe that the resveratrol is extracted from the wine. And like santabarbarian says, I believe that it can be purchased in capsule form. When I did a search for "resveratrol capsules" many "opportunities" popped right up. I have heard about the alleged merits of resveratrol for decades so it is great to learn that it is being studied.

As with any supplement, care should be taken to try to identify a reputable purveyor. And it goes without saying that clearing such with your care providers is a good idea.

BRCA Mutation, Preventive Surgery, and Osteoporosis

— Researchers advocate for increased hormone therapy for high-risk women

Bone health suffered in women with a BRCA mutation who underwent preventive oophorectomy, Canadian researchers reported.

Premenopausal women with the BRCA1 or BRCA2 mutation experienced a significant decline in bone mineral density (BMD) after undergoing prophylactic bilateral salpingo-oophorectomy...

"These pre-menopausal women looked a lot like post-menopausal women after a year following surgery,"

...use of hormonal therapy was able to offset most of the deleterious bone changes in both pre- and post-menopausal women after surgery.

"There are no standardized guidelines for the management of bone health in this population after surgery,"

"Given the important role of estrogen in maintaining various physiological functions, including bone health, this rate of hormone therapy use is far too low," the researchers stated, suggesting that the "mitigating effects" of hormone therapy use in this population should be noted in future clinical practice guidelines.

...suggested recommending enough calcium intake for this population, as well as engaging in weight-bearing exercise and exogenous hormone use for those for whom it is not contraindicated.

future studies with a longer follow-up period are needed to truly estimate the impact of prophylactic bilateral salpingo-oophorectomy on fracture risk in this high-risk population of women.

https://www.medpagetoday.com/endocrinology/osteoporosis/81507?xid=nl_mpt_DHE_2019-08-09&eun=g1278169d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily%20Headlines%202019-08-09&utm_term=NL_Daily_DHE_Active

Primary Source

JAMA Network Open

Source Reference: Kotsopoulos J, et al "Changes in Bone Mineral Density After Prophylactic Bilateral Salpingo-Oophorectomy in Carriers of a BRCA Mutation" JAMA Netw Open 2019; DOI: 10.1001/jamanetworkopen.2019.8420.

Validation of Microsatellite Instability Detection Using a Comprehensive Plasma-Based Genotyping Panel

Another liquid biopsy showed good correlation with tissue biopsy, this time for detection of microsatellite instability, which can influence treatment decisions for multiple types of cancer. (American Association for Cancer Research)

Conclusions: cfDNA-based MSI detection using Guardant360 is highly concordant with tissue-based testing, enabling highly accurate detection of MSI status concurrent with comprehensive genomic profiling and expanding access to immunotherapy for patients with advanced cancer for whom current testing practices are inadequate.

https://www.aacr.org/Newsroom/Pages/News-Release-Detail.aspx?ItemID=1328

https://clincancerres.aacrjournals.org/content/early/2019/08/02/1078-0432.CCR-19-1324#

DOI: 10.1158/1078-0432.CCR-19-1324

{Lots of breaking news on liquid biopsies. I don't believe that this one has been posted before.}

New 'don't eat me' signal may provide basis for cancer therapies

Cancer cells are known to protect themselves using proteins that tell immune cells not to attack them. Stanford researchers have discovered a new "don't eat me" signal, and blocking it may make cancer cells vulnerable to attack by the immune system.

... they implanted human breast cancer cells in mice. When CD24 signaling was blocked, the mice's scavenger macrophages of the immune system attacked the cancer.

Of particular interest was the discovery that ovarian and triple-negative breast cancer, both of which are very hard to treat, were highly affected by blocking the CD24 signaling. "This may be a vulnerability for those very dangerous cancers,"

http://med.stanford.edu/news/all-news/2019/07/new-dont-eat-me-signal-may-provide-basis-for-cancer-therapies.html

Medicare to Cover Pricey Cancer Tx Nationwide

Ups reimbursement to 65% and allows for guideline-recommended off-label use

The Centers for Medicare & Medicaid Services (CMS) on Wednesday announced nationwide coverage of an exciting but also very expensive new cancer treatment -- chimeric antigen receptor (CAR) T-cell therapy -- for Medicare recipients with certain types of lymphoma and for any expanded indications down the round.

Prior to the decision, coverage for CAR-T therapy carried uncertainty and was decided by regional Medicare administrators.

{Complicationg factor:} CMS has now put providers in a difficult position.

"They are required to provide this therapy, but the Administration is providing very little help to cover its high costs," Silverstein said. "The Administration's final inpatient rule, announced last week, does not do enough to adequately reimburse institutions for the cost of care or the cost of the product."

https://www.medpagetoday.com/publichealthpolicy/medicare/81492?xid=nl_mpt_DHE_2019-08-09&eun=g1278169d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily%20Headlines%202019-08-09&utm_term=NL_Daily_DHE_Active

https://www.cms.gov/newsroom/press-releases/trump-administration-makes-car-t-cell-cancer-therapy-available-medicare-beneficiaries-nationwide

{This article reminded me of Judy Perkins, the stage 4 breast cancer patient who remains cancer free 2 years after treatment with a new, experimental treatment. It is my understanding that that therapy used her T-calls but was a different technique. "CAR-T only works in blood cancers.... A different tactic is needed for solid tumors, such as breast cancer. And even though it is very expensive and very complicated, CAR-T can be successful, he noted. "It's a whole different way of thinking about cancer treatment," It is encouraging that CAR-T is now being covered by Medicare.}

{quote from https://www.nbcnews.com/health/health-news/highly-personalized-treatment-saves-breast-cancer-patient-n879841}

Results From the First Multicenter, Open-label, Phase IIIb Study Investigating the Combination of Pertuzumab With Subcutaneous Trastuzumab and a Taxane in Patients With HER2-positive Metastatic Breast Cancer (SAPPHIRE)

The primary objective of this study was to assess the safety and tolerability of combination pertuzumab, subcutaneous trastuzumab (Herceptin), and investigator's choice of taxane chemotherapy in previously untreated patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. Efficacy was a secondary objective.

This study was an open-label, non-randomized study of patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who had no previous systemic non-hormonal anti-cancer therapy for metastatic disease. The primary endpoints included adverse events (AE), serious AEs, and cardiac AEs. Secondary endpoints included overall response rate, progression-free survival, and overall survival. Patients were treated with pertuzumab and subcutaneous trastuzumab in 3-weekly cycles with taxane chemotherapy until disease progression, unacceptable toxicity, or withdrawal of consent and followed for a minimum of 24 months from initiation of study treatment.

Subcutaneous trastuzumab in this combination has an acceptable safety and tolerability profile, including cardiac safety profile. Safety and efficacy appear similar to previous studies of intravenous trastuzumab in this combination.

https://www.clinical-breast-cancer.com/article/S1526-8209(18)30696-7/fulltext

DOI: https://doi.org/10.1016/j.clbc.2019.02.008

Tracking Candida auris

Candida auris is an emerging fungus that presents a serious global health threat. C. auris causes severe illness in hospitalized patients in several countries, including the United States. Patients can remain colonized with C. auris for a long time and C. auris can persist on surfaces in healthcare environments. This can result in spread of C. auris between patients in healthcare facilities.

Most C. auris cases in the United States have been detected in the New York City area, New Jersey, and the Chicago area. Strains of C. auris in the United States have been linked to other parts of the world. U.S. C. auris cases are a result of inadvertent introduction into the United States from a patient who recently received healthcare in a country where C. auris has been reported or a result of local spread after such an introduction.

Candida auris was made nationally notifiable at the 2018 Council for State and Territorial Epidemiologists (CSTE) Annual Conference. For the updated case definition and information on the nationally notifiable condition status, please see the 2018 CSTE position statement.

CDC encourages all U.S. laboratories that identify C. auris to notify their state or local public health authorities and CDC at candidaauris@cdc.gov. CDC is working closely with public health and healthcare partners to prevent and respond to C. auris infections. The CDC-sponsored Antibiotic Resistance Laboratory Network (ARLN) will help improve detection and response to C. auris nationwide.

{This is rather technical but strains of multi-drug resistant C. auris have been identified in the U.S. The public should be aware and those with compromised immune systems may wish to take note.}

https://www.cdc.gov/fungal/candida-auris/tracking-c-auris.html

https://www.cdc.gov/fungal/candida-auris/index.html

https://www.cdc.gov/drugresistance/solutions-initiative/stories/cdc-response-to-global-threat.html

AZ announces Phase I DS-8201 results

AstraZeneca has announced two Lancet Oncologypublications of its Phase I dose-expansion results of DS-8201 (trastuzumab deruxtecan) in HER2-positive metastatic breast and gastric cancer.

The breast cancer trial found a confirmed objective response rate of 59.5% and a disease control rate of 93.7% at a recommended expansion dose of 5.4 or 6.4 mg/kg. There was also a 20.7 months median duration of response in HER2-positive metastatic breast cancer patients previously treated with trastuzumab emtansine... Patients enrolled in this part of the trial had a median of seven prior lines of treatment, including trastuzumab and trastuzumab emtansine, and in 86% of cases, pertuzumab.

"For patients with HER2-positive metastatic breast cancer that progresses after trastuzumab, pertuzumab, and trastuzumab emtansine, optimal treatment is not clearly defined and choices may be limited. These results demonstrate preliminary clinically-meaningful response rates with an impressive duration of response, supporting further development and suggesting a potential role for trastuzumab deruxtecan as a HER2-targeted therapy option in this setting,"

http://www.pharmatimes.com/news/az_announces_phase_i_ds-8201_results_1286498?fbclid=IwAR3a2M8mR-6CBJ7nX9gJO4T55X6ERRQjo8Oj5zBYIhTwZP8r92MPuC3OfSc

Long-Term Comparison of Aesthetical Outcomes After Oncoplastic Surgery and Lumpectomy in Breast Cancer Patients

Lumpectomy may result in major deformities and asymmetries in approximately one-third of patients. Although oncoplastic surgery (OP) could be a useful alternative to avoid them, lack of strong data is causing some debate. The purpose of this study was to compare aesthetic outcomes in patients undergoing OP versus lumpectomy using three different assessment methods.

Methods

A total of 122 patients were included in this cross-sectional multicentric study; 57 underwent OP (46.7 %), and 65 underwent lumpectomy (53.3 %). Two breast surgeons and two plastic surgeons from different institutions using the Garbay scale independently evaluated aesthetic outcomes. BCCT.core software was applied in both groups, and the patients evaluated their aesthetic outcomes answering a questionnaire about their satisfaction rate.

Results

OP group had a higher proportion of excellent aesthetic results according to the BCCT.core software analysis (p = 0.028) and the specialists (p = 0.002). Multifactorial analyses showed that age ≥70 years (RP = 6.02; 95 % confidence interval [CI] 1.73–21.0; p = 0.005), tumors in the medial, inferior, and central quadrants (RP = 4.21; 95 % CI 1.88–9.44; p < 0.001), and large breasts (RP = 7.55; 95 % CI 2.48–23.0; p < 0.001) were significant risk factors for poor aesthetic outcomes after lumpectomy. The patients classified their results as better than those by the specialists and by the software, with no statistical difference between the groups.

Conclusions

Excellent aesthetic results were more frequent in the OP group according to BCCT.core software analysis and specialists. In addition, some clinical conditions and tumor locations in the breast can be considered risky factors for poor aesthetic outcomes in lumpectomy.

https://link.springer.com/article/10.1245%2Fs10434-014-4301-6#citeas

https://doi.org/10.1245/s10434-014-4301-6