Breaking Research News from sources other than Breastcancer.org

Lumpie

Impact of Subtype on Survival of Young Patients With Stage IV Breast Cancer

• In this study of SEER data, 6302 patients with de novo stage IV breast cancer who were <60 years of age were identified and assessed to determine differences in overall survival based on age and disease subtype. Patients <40 years had a significantly higher proportion of HER2+ cancer, a lower proportion of HR+/HER2− disease, and significantly longer median overall survival (45 months vs 33 months) compared with patients aged 40 to 59 years with the exception of those with triple-negative disease.

• Additional studies are warranted to investigate potential underlying mechanisms.
• Compared with those aged 40 to 59 years, patients with de novo metastatic breast cancer aged < 40 years experienced significantly longer survival, except in the setting of triple-negative disease. Distinct treatment-related or biological factors may exist between earlier stage and metastatic breast cancers; further examination of the potential reasons for our findings are warranted.
• https://www.practiceupdate.com/c/80274/67/13/?elsc...
• https://www.clinical-breast-cancer.com/article/S15...(18)30604-9/fulltext
• DOI: https://doi.org/10.1016/j.clbc.2019.01.005

LaurenH

Lumpie - thanks for continuously posting such great stuff. Saw this one this morning and thought it would be good to also share here:

https://www.dana-farber.org/newsroom/

Basically this says there is evidence that taking a break from Ibrance may reverse resistance, which is pretty exciting

thecargirl

Hi santabarbarian,

What maintenance dose of Metfomin does your Dr. have you on?

Thanks,

Susan

santabarbarian

I am taking 500 mg twice a day, am and pm. So 1000 total.

thecargirl

Thank-you,

Susan

Lumpie

Should Medicare Part B Drugs Get Budget Cap?

MedPAC commissioners discuss ways to lower prices in the program

March 08, 2019

Should there be a cap on Medicare's Part B drug budget? That was one of the options that members of the Medicare Payment Assessment Commission (MedPAC) mentioned here Thursday in a discussion of pricing alternatives.

The binding arbitration model (known as "baseball arbitration") could be used for products with limited competition that exceed a specified cost threshold...

...this model also has the advantage of potentially lowering prices for beneficiaries and taxpayers, although some people may raise concerns about access to drugs if manufacturers decide not to participate in arbitration, which would mean Medicare couldn't cover the drug.

"there is some real danger in treating similar drugs for payment purposes as equivalent for effectiveness and side effects, so I want to be clear there's an ability to provide appropriate treatment,"

The commission did not take any vote on the drug pricing proposals; commission staff will continue working on the issue and it may appear in MedPAC's June report, a spokesman said.

https://www.medpagetoday.com/publichealthpolicy/me...

Lumpie

Immunotherapy Wins First FDA Approval in Breast Cancer

Atezolizumab OK'd for PD-L1-positive triple-negative disease

March 8, 2019

The FDA granted accelerated approval to atezolizumab (Tecentriq) for advanced triple-negative breast cancer (TNBC), marking the first immunotherapy with a breast cancer indication.

The PD-L1 checkpoint inhibitor was approved in combination with nab-paclitaxel (Abraxane) for metastatic or locally advanced, unresectable TNBC, according to the announcement from Genentech, manufacturer of atezolizumab.

In the PD-L1-positive patients, progression-free survival (PFS) in the atezolizumab arm was 7.4 months compared with 4.8 months in the placebo arm

Response rates in the PD-L1-positive patients were 58.9% with atezolizumab and 42.6% with placebo. Median duration was 8.5 versus 5.5 months, respectively.

Under the conditions of accelerated approval, full approval will rest upon confirmatory trial data.

The most common grade 3/4 AEs (≥2%) include low red and white blood cell counts, decreased neutrophil counts, fatigue, increased aspartate transaminase levels, low blood potassium levels, neuropathy, and pneumonia.

https://www.medpagetoday.com/hematologyoncology/br...

Lumpie

Vaccine Prolongs Remission in Triple-Negative Breast Cancer

Effect in hard-to-treat subgroup "clinically meaningful"

Treatment with a novel peptide vaccine appeared to delay disease recurrence in triple-negative breast cancer (TNBC) patients with low HER2 expression, a subgroup analysis of a phase II trial found.

At a median follow-up of 26.1 months, disease recurrence occurred in 7.5% of TNBC patients who received nelipepimut-S (NeuVax) compared with 26.7% in the control arm

In the NeuVax and control arms, respectively, rates of disease-free survival (DFS) among the 97 TNBC patients were:

• 92.6% versus 70.2% at 24 months

• 82.3% versus 70.2% at 36 months

https://www.medpagetoday.com/meetingcoverage/addit...

TectonicShift

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tessu

Thanks, Lumpie, for keeping us up to date!

Minniesi

I can't seem to post links here, so you can find this study with search? If someone else can link the study from nature.com and post it here?

Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy

Combining three drugs (METFORMIN+VENETOLAX+PD-1), they got great and durable results in this study, next clinical trials on patients:

" A two-step treatment regimen, beginning with neoadjuvant metformin+venetoclax to induce apoptosis and followed by adjuvant metformin+venetoclax+anti-PD-1 treatment to overcome immune escape, led to durable antitumor responses even after drug withdrawal. We demonstrate that pharmacological reactivation of MYC-dependent apoptosis is a powerful antitumor strategy involving both tumor cell depletion and immunosurveillance."

"We show that the strong induction of apoptosis by ABv treatment (metformin+venetoclax) increases the density of tumor-infiltrating lymphocytes (TILs). "

"In support of this notion, administration of anti-PD-1 antibody alone did not inhibit tumor growth at all but showed remarkable efficacy when administered together with ABv treatment."

"In summary, we report here the discovery and preclinical validation of a clinically applicable synthetic-lethal MYC-targeted therapeutic strategy for the treatment of breast cancer. The ABv+anti-PD-1 combination showed remarkable efficacy in a number of breast cancer models, which was somewhat surprising in light of the fact that BCL-2 dependency is most often observed in hematologic malignancies. The applicability of the ABv+anti-PD-1 combination for treating other cancer types with high MYC and BCL-2/BCL-XL status is currently being investigated in preclinical models."

Lumpie

Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy

Published: 06 February 2019 (correction published 20 Feb 2019)

Abstract: Elevated MYC expression sensitizes tumor cells to apoptosis but the therapeutic potential of this mechanism remains unclear. We find, in a model of MYC-driven breast cancer, that pharmacological activation of AMPK strongly synergizes with BCL-2/BCL-XL inhibitors to activate apoptosis. We demonstrate the translational potential of an AMPK and BCL-2/BCL-XL co-targeting strategy in ex vivo and in vivo models of MYC-high breast cancer. Metformin combined with navitoclax or venetoclax efficiently inhibited tumor growth, conferred survival benefits and induced tumor infiltration by immune cells. However, withdrawal of the drugs allowed tumor re-growth with presentation of PD-1+/CD8+ T cell infiltrates, suggesting immune escape. A two-step treatment regimen, beginning with neoadjuvant metformin+venetoclax to induce apoptosis and followed by adjuvant metformin+venetoclax+anti-PD-1 treatment to overcome immune escape, led to durable antitumor responses even after drug withdrawal. We demonstrate that pharmacological reactivation of MYC-dependent apoptosis is a powerful antitumor strategy involving both tumor cell depletion and immunosurveillance.

https://www.nature.com/articles/s41467-019-08541-2

Nature Communicationsvolume 10, Article number: 620 (2019)

(Cannot locate a DOI. Sorry)

Thanks for providing a prompt to this article Minniesi.

Lumpie

Genetic Testing Recommended for All Patients With Breast Cancer

All with personal history of breast cancer should be offered testing; updated testing recommended

Genetic testing should be made available to all patients with a history of breast cancer, according to an updated consensus guideline from the American Society of Breast Surgeons (ASBS).

Researchers from the ASBS outlined recommendations for genetic testing that medical professionals can use for assessing hereditary risk for breast cancer. Data were included from large datasets, basic science publications, and recent updated national guidelines.

"Our society has a responsibility to act when we see an opportunity to decrease unnecessary morbidity and mortality," Walton Taylor, M.D., president of the American Society of Breast Surgeons, said in a statement. "We do so today with the adoption of our new position on this issue."

The Society's updated statement was developed by the panel members listed {link below}, and on February 10, 2019, was approved by the {American Society of Breast Surgeons} Board of Directors.

https://www.practiceupdate.com/C/80788/56?elsca1=e...

https://www.breastsurgeons.org/about/statements/PD...

Lumpie

Adjuvant Chemotherapy for ER+ Breast Cancer -

A Sea Change Is Underway

Adjuvant breast cancer treatments—chemotherapy, human epidermal growth factor receptor 2 (HER2)–targeted therapies, and endocrine therapy—prevent recurrence and extend survival. Unfortunately, because risk assessment is imprecise and treatments are not uniformly effective, many women are treated to benefit a small number. Chemotherapy has the most onerous short-term side effects and is the treatment that patients most wish to avoid.

Over the past 15 years, multiple genomic assays have been developed that more precisely characterize the risk of developing recurrent breast cancer.

...use of adjuvant chemotherapy for patients with stage I–II ER+/HER2- disease declined from 26.6% to 14.1% and 81.1% to 64.2% among node-negative and node-positive patients, respectively, between 2013 and 2015.

With the advent of targeted therapy for breast cancer, both oncologists and their patients appear less willing than in the past to take a toxic treatment for a very small benefit.

...a National Comprehensive Care Network database study demonstrated excellent outcomes for patients with small ER+/HER2- tumors not treated with chemotherapy with distant recurrence-free survival rates of 98% (T1a) and 96% (T1b). These data suggest that most patients with small ER+ tumors should not receive chemotherapy and may have also led to a decline in chemotherapy use.

Genomic expression assays may ultimately have an even greater impact on the management of young women with ER+ breast cancer, a population that faces the long-term consequences of treatment toxicities.

Whether we are focusing on traditional chemotherapy or targeted approaches, we must strive to integrate prognostic biomarkers such as pathologic complete response and develop new prognostic and predictive biomarkers. Our goal is to provide the adjuvant treatment that allows each patient to remain cancer free and, at the same time, avoid unnecessary toxicity.

https://www.medscape.com/viewarticle/896998?src=mk...

Philip D. Poorvu; Eric P. Winer

J Natl Cancer Inst. 2018;110(5):443-445. © 2018 Oxford University Press

Lumpie

Patient recommendations for reducing long‐lasting economic burden after breast cancer

First published: 06 March 2019

Journal: Cancer

In the United States, patients who have breast cancer experience significant economic burden compared with those who have other types of cancers. Cancer‐related economic burden is exacerbated by adverse treatment effects. Strategies to resolve the economic burden caused by breast cancer and its adverse treatment effects have stemmed from the perspectives of health care providers, oncology navigators, and other subject‐matter experts. For the current study, patient‐driven recommendations were elicited to reduce economic burden after 1) breast cancer and 2) breast cancer‐related lymphedema, which is a common, persistent adverse effect of breast cancer.

Of 40 interviewees (mean age, 64 years; mean time since diagnosis, 12 years), 27 offered recommendations to reduce the economic burden caused by cancer and its adverse treatment effects. Nine recommendations emerged across 4 major themes: expanding affordable insurance and insurance‐covered items, especially for lymphedema treatment (among the 60% who reported lymphedema); supportive domestic help; financial assistance from diagnosis through treatment; and employment‐preserving policies.

The current study yielded 9 actionable, patient‐driven recommendations—changes to insurance, supportive services, financial assistance, and protective policies—to reduce breast cancer‐related economic burden. These recommendations should be tested through policy and programmatic interventions.

https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.32012

https://doi.org/10.1002/cncr.32012

Read BCO coverage here: https://www.breastcancer.org/research-news/dx-women-offer-advice-on-financial-burden

Lumpie

Unusual mechanism of CDK4/6 inhibitor resistance found, may be reversible

Breast cancer cells can acquire resistance to the relatively new drugs known as CDK4/6 inhibitors by producing higher amounts of CDK6, a cell cycle protein, a new study has found, and those cells can transfer their resistant traits to other cancer cells via molecular carriers called exosomes.

This drug resistance mechanism, identified by researchers at Dana-Farber Cancer Institute, is highly unusual, they said, and laboratory studies suggest it may be reversible. Breast cancer cells that developed resistance to a CDK4/6 inhibitor, palbociclib, became sensitive to the drug again after a "treatment holiday" of several weeks when no palbociclib was administered, they said in an article in Cell Reports.....

Experiments showed that cancer cells' resistance to palbociclib could be reversed by stopping treatment with the drug for seven weeks. The treatment "holiday" was tested in mice as well: palbociclib-resistant tumor material was implanted into animals, who were treated with the drug until resistant tumors were established. The drug was then discontinued for 28 days, and after treatment was started again, the tumors shrank.

The discovery that resistance to a CDK4/6 inhibitor is transmitted to tumor cells via exosomes has a potential benefit for patient management, the scientists said. "We may be able to examine patients' exosomes [by means of a blood test] and see if they are becoming resistant earlier than would be apparent because the cancer progressed on radiographic scans," said Shapiro.

Posted on MARCH 05, 2019

https://www.dana-farber.org/newsroom/news-releases/2019/unusual-mechanism-of-cdk4/6-inhibitor-resistance-found--may-be-reversible/?fbclid=IwAR25N3Ms297BuzjWWzOfCQahjNxZOgrcYATopBHgbI50WsXqKCqhIPTfD1c

Lumpie

New Trials Recently Added to BCT and MTS (March 2019)

Carefully Selected News and Features About Metastatic Breast Cancer Research

Powered by BreastCancerTrials.org

Below are MBC trials that have been added to BreastCancerTrials.org (BCT) in the last month. These trials can also be found on Metastatic Trial Search (MTS)

All MBC

• • Radiation Therapy With or Without Olaparib For Inflammatory Breast Cancer
  • CSF in Treating Chemotherapy Induced Neutropenia (TrACER)
  • Targeted Therapy Rebastinib With Carboplatin for Advanced Breast Cancer
  • Syndros to Reduce Pain from Bone Metastases in Stage IV Breast Cancer

Triple Negative

• • Immunotherapy Galinpepimut-S and Pembrolizumab for Advanced Triple Negative Breast Cancer
  • Immunotherapy and Chemotherapy Before Surgery to Treat Triple Negative Breast Cancer

HER2 Positive (HER2+)

• • T-DM1 and Palbociclib for Metastatic HER2 Breast Cancer (T-DM1)

HER2 Low or Negative

• • DS-8201a for HER2-low Advanced Breast Cancer (DESTINY)

Use Metastatic Trial Search to find all metastatic breast cancer trials that are right for you.

https://metastatictrialtalk.org/2019/03/02/new-trials-9/

{You can sign up for free, periodic updates on MBC clinical trials and updates similar to this at https://metastatictrialtalk.org/}

Lumpie

Expert Discusses the Role of Liquid Biopsies in Breast Cancer

Published Online:4:16 PM, Mon November 5, 2018

The use of next-generation sequencing (NGS) has the potential to improve the treatment of patients with breast cancer, but there are some challenges that still need to be overcome...

"It's not just a matter of the assay itself," Sparano added. "It's a matter of the assay and the limited number of drugs we have available to treat tumors associated with specific molecular alterations."

In an interview with Targeted Oncology, Joseph A. Sparano, MD, associate director for clinical research, Albert Einstein Cancer Center, Montefiore Medical Center, discussed the potential for liquid biopsy and the ongoing challenge of improving survival for patients with metastatic disease.

https://www.targetedonc.com/news/expert-discusses-the-role-of-liquid-biopsies-in-breast-cancer

{Brief interview discusses liquid biopsies in Q and A format.}

Traveltext

This is a very important research paper that one of the authors has very kindly given me full access to.

"Our findings thus address one of the contemporary challenges in breast oncology, namely identification of the subset of ER-positive patients who have a high risk of recurrence and tumour biomarkers that are more predictive of recurrence than are standard clinical covariates."

In other words, predictions of long-term recurrence can be made for those of us who are ER+/HR+ HER2 -

https://www.nature.com/articles/s41586-019-1007-8....

Palesa2018

This study suggests that there is no benefit to Vit D3 supplementation. Yet there are so many others that suggest a strong link between recurrence prevention and Vit D3. I will continue taking my supplements.

http://www.practiceupdate.com/content/vitamin-d-su...

santabarbarian

The dose they looked at is less than half the dose my MO recommended (5000 IU/day).

Ingerp

Traveltext--thanks for posting that link. I ran into the firewall, but found this article about the study:

https://www.sciencedaily.com/releases/2019/03/190313143243.htm

Rah2464

Ingerp - thanks for posting this. I am so hopeful that this work continues and those who follow after us have clearer information on how to battle this disease.

Ingerp

Rah2464 I know the science gets better and better. I came home from a Herceptin infusion last Friday to read that the FDA has <finally> approved a subcutaneous version. It won't be long before women will get a simple shot rather than an IV or port access (like they've been doing for quite a while in Europe). It won't happen in time to help me but I am grateful for the treatments we currently have and optimistic about the future as research continues.

Lumpie

Access to CAR T-Cell Therapies for Medicare Patients

"There is currently no national Medicare policy for covering CAR T-cell therapies. Thus far local Medicare Administrative Contractors (MACs) have discretion over whether to pay for these therapies. In the absence of a national coverage determination (NCD), MACs are empowered to make local coverage determinations (LCD). They are the front line for Medicare patients within their geographic area. Under the new National Coverage Analysis (NCA) memo from CMS, Medicare would cover CAR T-cell therapies under CED across the United States. This would include a patient registry where data are collected on the patient for a two year period. These data would include both clinical characteristics as well as patient reported outcome data."

https://www.cancersupportcommunity.org/blog/2019/03/access-car-cell-therapies-medicare-patients?utm_source=CPI+March+Newsletter&utm_medium=email&utm_campaign=CPIMarNLemail&utm_content=CartCEDbutton

april1964

...just saw this:

Study in mice examines impact of reused cooking oil on breast cancer progression

https://www.eurekalert.org/pub_releases/2019-03/uo...

Palesa2018

April1964 thanks for this. Very sobering. On the odd occasion I indulge in fries and who knows about the oil used in restaurants.

Thanks to all who post on this this thread. It is appreciated.

april1964

... I think this was a mouse study ... who knows how it translates to humans

april1964

I’m not giving up fries!

Lumpie

april1964: I hear ya! It's all about quality of life! (But I must say, that article was sobering.)