Breaking Research News from sources other than Breastcancer.org

Karenfizedbo15

Just for info, as this pertains to those of us moving into second line treatment where it seems we can’t access Faslodex in combo with a Cdk4/6 inhibitor if we’ve already had an inhibitor...

Scotland backs Pfizer's Ibrance for breast cancer

Phil TaylorJuly 11, 2019

Pfizer's Ibrance has been approved for use by the NHS in Scotland as a second-line treatment for advanced breast cancer after hormonal therapy.

The Scottish Medicines Consortium (SMC) said Ibrance – a CDK4/6 inhibitor – can increase the time before the condition progresses and delay the need for chemotherapy in people with hormone receptor-positive, HER2-negative advanced breast cancer.

Pfizer's drug was backed for use alongside anti-oestrogen drug fulvestrant for these patients under the SMC's Patient and Clinician Engagement (PACE) process, which is used for medicines to treat end of life and very rare conditions.

It is estimated that around 400 women could be eligible for treatment with the drug each year in Scotland. South of the border in England, the National Institute for Health and Care Excellence (NICE) is still deliberating on this use for Ibrance with a decision due before the end of the year.

At a PACE meeting to discuss Ibrance, patient groups and clinicians said that this stage of breast cancer is incurable and treatment options are limited.

"We know that this approval from the SMC will be meaningful for the many patients and families who are affected by this type of advanced breast cancer," said Pfizer UK's oncology medical director Dr Olivia Ashman. "We hope the same outcome will be reached by NICE later this year."

In the PALOMA-3 trial, Ibrance was shown to increase the time before the condition progresses, allowing patients additional months of life, and could also delay the need for chemotherapy with its associated side effects.

Ibrance has been approved for NHS use in Scotland since December 2017, when the SMC gave the green light for restricted prescribing of the drug in first-line HR+/HER2- breast cancer in combination with aromatase inhibitor drugs.

First-line use of the drug south of the border was rejected by NICE earlier that year but given the nod after Pfizer agreed a price reduction. Two other CDK4/6 inhibitors – Novartis' Kisqali(ribociclib) and Eli Lilly's Verzenios (abemaciclib) have also been approved by the SMC and NICE for first-line use.

Both are also trying to get the okay for second-line use with fulvestrant. Kisqali was turned down by NICE for this use in April and is still under review by the SMC with a verdict due later this year. Verzenios meanwhile has been approved in England for previously-treated patients, but only via the Cancer Drugs Fund.

Ibrance was the first CDK4/6 inhibitor to reach the market and is already a blockbuster with sales of around $4 billion last year. It is predicted to swell to $6 billion by 2022, staying well ahead of its rivals although both Novartis and Lilly's drugs are expected to compete closely for second place in the market.

Earlier estimates by EvaluatePharma give Kisqali the edge over Lilly's drug with predicted sales of $1.6 billion in 2022, with Verzenios not expected to be far behind.

debbew

[Early research in vitro and mice]

Calcium bursts kill drug-resistant tumor cells

Multidrug resistance (MDR)—a process in which tumors become resistant to multiple medicines—is the main cause of failure of cancer chemotherapy. Tumor cells often acquire MDR by boosting their production of proteins that pump drugs out of the cell, rendering the chemotherapies ineffective. Now, researchers reporting in ACS' Nano Letters have developed nanoparticles that release bursts of calcium inside tumor cells, inhibiting drug pumps and reversing MDR...

The researchers made a "calcium ion nanogenerator" (TCaNG) by loading calcium phosphate nanoparticles with the chemotherapy drug doxorubicin and then coating them with molecules that would allow TCaNG to target and enter cancer cells. Once inside cells, TCaNGs entered an acidic compartment, where the TCaNGs disintegrated, releasing both doxorubicin and bursts of calcium ions. When the team tested TCaNG on cancer cells in a petri dish in the lab, both ATP and P-gp production decreased, which allowed doxorubicin to kill the previously resistant tumor cells. When tested in tumor-bearing mice, TCaNG-treated mice showed significantly smaller tumors after 21 days of treatment than control mice, with no apparent side effects.

https://phys.org/news/2020-10-calcium-drug-resista...

DOI: 10.1021/acs.nanolett.0c03042

BlueGirlRedState

From the journal of International Journal of Clinical Oncology, potential biomarkers to evaluate effectiveness of Ibrance / CDK4/6 inhibitor.

https://breast-cancer-research.biomedcentral.com/a...

debbew

[Early, basic research]

Breast cancer study uncovers new RNA targets for treatment and diagnostics

The team discovered that two lncRNAs named TROLL-2 and TROLL-3 are associated with the progression of breast cancer. Tamping them down inhibited breast cancer formation in mice...

They went on to show that when Tap63 is downregulated, there's a complex interplay between the lncRNAs and other proteins, including one called WDR26. That stimulates AKT signaling, promoting the development of invasive breast tumors....

The researchers believe their findings could be used in several ways to diagnose and treat cancer. For example, they could help predict which patients are likely to respond to AKT inhibitors. There are several in development, including Roche's ipatasertib, which the company is testing in breast and prostate cancers.

There could be treatment applications, as well, said Elsa Flores, Ph.D., who leads Moffit's department of molecular oncology and cancer biology and evolution program. The findings could point to targets for "therapies against metastatic cancers with alterations in TP53 and hyperactivation of the PI3K/AKT pathway," Flores said in a statement.

https://www.fiercebiotech.com/research/breast-canc...

ShetlandPony

News you can use:

From AACR Annual Meeting 2020

“...Circadian melatonin signal disruption by exposure to artificial light at night promotes bone lytic breast cancer metastasis"

https://cancerres.aacrjournals.org/content/80/16_Supplement/LB-212

A good plain-language summary is here:

https://foodforbreastcancer.com/

Bottom line: Sleeping in a very dark room may help prevent mets. Melatonin supplements If needed may be a good thing.

Anonymous

Studies have shown that women who work night shift have a higher incidence of breast cancer and now this.

I am definitely in this category...staying up all night , falling asleep with tv on, laying in bed restless looking at my tablet, etc.

Have been like this for years prior to diagnosis. Just recently was able to adjust my sleep schedule after another year of tossing and turning til 5 am. I am holding on for dear life, holding on to being able to fall asleep in the dark and wake up at sunrise.

And with that...good night

Anonymous

olms61 - I hope you slept well!

This article is scary about COVID-19 and cancer. “Patients with cancer and COVID-19 have a higher risk of severe disease and mortality, researchers reported.“

“If the patient was neutropenic, the mortality was very high -- six of nine died.”😳

I have been slightly neutropenic for a year. I also was planning to have all the kids for Thanksgiving. COVID +Cancer sucks.
https://www.medpagetoday.com/meetingcoverage/chest...

Dee

Anonymous

Dee, thank you, I slept pretty well and had to get up early for my infusion today. All good.

Yes, COVID just makes our already complicated lives exponentially more complicated. Praying for a resolution to this and soon.

morrigan_2575

yeah it's never a good time to get Cancer but, Cancer+COVID sucks.

buttonsmachine

Thank you for posting that, Dee. I have sent the article along to a few people in my life who need to know that information. :-)

santabarbarian

Shetland the recommendation I got was 1. to black out all lights in bedroom, 2. to take 20mg (--work up to this slowly!) of melatonin at roughly the same time each night, and 3. to keep my BR cold. You can have all the blankets you want but the room itself should be cold (under 68 ideally). I believe the cold promotes the production of brown (metabolically active) fat.

Circadian rhythms govern the 'wake/sleep' cycles of cancer cells, too, and this can influence when the drugs are the most effectively administered. ('Chronomodulation')

Lumpie

Accuray announces ClearRT Helical kVCT Imaging For #Radixact - 510(k) pending

Note: this is a marketing piece. Long on images, short on details.

Provides some information on improved imaging soon to be available from Accuray, U.S. based makers of CyberKnife, one of the frequently used tools for SRS (Stereotactic radiosurgery).

Lumpie

Efficacy and Safety of Chloroquine in Combination With Taxanes for Advanced or Metastatic Anthracycline-Refractory Breast Cancer

October 24, 2020

Published in Clinical Breast Cnacer

• The authors of this small phase II study evaluated combination treatment with chloroquine and taxane or taxane-like chemotherapy in women with locally advanced or metastatic breast cancer refractory to anthracycline-based chemotherapy. The overall response rate of 45% exceeded the expected benchmark of 30%, and the median progression-free and overall survivals were 12 and 25 months, respectively. The combination was well-tolerated, with a rate of 13% of grade 3+ adverse events.
• Larger studies are warranted to evaluate this combination.

https://www.practiceupdate.com/C/107842/56?elsca1=...

https://linkinghub.elsevier.com/retrieve/pii/S1526...

DOI:https://doi.org/10.1016/j.clbc.2020.09.015

{Free access to practice update. Registration may be required. Free access to abstract. Fee or subscription for access to full article.}

BSandra

Chloroquine is gaining some recognition in combo with taxanes: https://www.practiceupdate.com/content/efficacy-an...

Saulius

Anonymous

Thought this was interesting.

High-Dose SBRT More Effective for Painful Spine Metastases

— Roughly one-third of patients had a complete pain response at 3 and 6 months

https://www.medpagetoday.com/meetingcoverage/astro/89346?xid=nl_mpt_DHE_2020-10-27&eun=g1627129d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily%20Headlines%20Top%20Cat%20HeC%20%202020-10-27&utm_term=NL_Daily_DHE_dual-gmail-definition

Also

MDACC has a trial for

Hydroxychloroquine, Palbociclib, and Letrozole Before Surgery in Treating Participants With Estrogen Receptor Positive, HER2 Negative Breast Cancer

https://clinicaltrials.gov/ct2/show/NCT03774472

Dee

JoynerL

Article for clinicians on various treatments options for bone mets. Very interesting, if technical:

settings Open AccessReview Diagnosis and Treatment of Bone Metastases in Breast Cancer: Radiotherapy, Local Approach and Systemic Therapy in a Guide for Clinicians

Anonymous

good article,Joyner. I printed it out to save. Thanks

BevJen

Lynn,

That was a great article about bone metastases. I had seen bits and pieces of the info in there in different articles, but not in such a consistent, complete way. I did note that this was a study headed up by the Europeans -- confirms my belief that we should look at what docs in other countries are doing as well as info about US progress in treating MBC.

I think I'm going to send this one to my MO. Maybe then she won't think I'm crazy when I ask her about local treatment for bone metastases -- the standard American protocol seems to be treatment for pain, only. This article goes beyond that.

Lumpie

Stereotactic radiosurgery may be new standard of care for four or more brain metastases

October 27, 2020

Stereotactic radiosurgery conferred equivalent OS as whole-brain radiation but with less cognitive decline in patients with four or more nonmelanoma brain metastases, according to study results presented at the virtual ASTRO Annual Meeting.

"Up to 30% of [patients with cancer] develop brain metastases at some point during the disease process and these patients typically do not do well with current treatment modalities, including radiation and surgery,"... "Whole-brain radiation has been around for some time now; however, it is associated with significant side effects, which is why within the past decade there have been tremendous efforts to minimize the cognitive side effects of brain radiation."

At median follow-up of 6.6 months, results showed patients in the stereotactic radiosurgery group scored higher on memory function compared with baseline, whereas patients in the whole-brain radiation group scored worse compared with baseline. Researchers observed a clinically meaningful and statistically significant benefit with radiosurgery at 1 month and 6 months.

Moreover, half of patients in the whole-brain radiation group experienced a clinically meaningful decline in cognitive function 4 months after treatment compared with only 6% of patients in the stereotactic radiosurgery group.

The radiosurgery and whole-brain radiotherapy groups had similar local control rates at 4 months, median OS and median time to distant brain failure. However, patients assigned radiosurgery experienced shorter interruptions of systemic therapy, with time to systemic therapy of 1.7 weeks vs. 4.1 weeks with whole-brain radiation.

"This is particularly important because patients with brain metastases often have metastases outside of the brain, as well," Li said. "When these patients receive whole-brain radiation, we typically hold chemotherapy for 2 weeks and we continue to hold systemic therapy for up to 4 weeks for them to wash out before they can return to systemic therapy. These patients often need systemic therapy to control extracranial disease."

Radiation necrosis occurred in 17% of patients in the radiosurgery group and in 4% of all treated lesions. Grade 3 or higher toxicities occurred among 8% of patients (n = 2) in the radiosurgery group and 15% of patients (n = 4) in the whole-brain radiation group.

"Despite early termination of the study and the use of memantine in the whole-brain radiation therapy arm, we were able to show that stereotactic radiosurgery was associated with reduced risk [for] cognitive deterioration compared with whole-brain radiation as demonstrated by a constellation of neurocognitive tests, individually or by composite scores," Li said. "The results from this randomized, phase 3 trial strongly support the use of stereotactic radiosurgery in patients with four to 15 brain metastases to better preserve cognitive function and to minimize interruption of systemic therapy, without compromising OS."

Stephanie E. Weiss, MD, FASTRO

Fox Chase Cancer Center

https://www.healio.com/news/hematology-oncology/20...

Source: Li J, et al. Abstract 41. Presented at: American Society for Radiation Oncology Annual Meeting (virtual); Oct. 25-28, 2020.

{Reporting available w/o charge, registration may be required.}

Lumpie

Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination–Related Genes

November 05, 2020 Journal of Clinical Oncology

• The authors of this phase II trial evaluated the PARP inhibitor olaparib in the treatment of 54 patients with metastatic breast cancer (76% ER-positive/HER2-negative) and either germline mutations in non-BRCA1/2 homologous recombination–related DNA repair genes (cohort 1) or somatic mutations in BRCA1/2 or other non-BRCA1/2 homologous recombination–related genes (cohort 2). The objective response rate (ORR) in cohort 1 and cohort 2 were similar (33% and 31%), but confirmed responses were only observed in patients with germline PALB2 (ORR, 82%; PFS, 13.3 months) and somatic BRCA1/2 (ORR 50%; PFS, 6.3 months) mutations.
• These findings appear to expand the patient population likely benefit from PARP inhibitors to include those with somatic BRCA1/2 and germline PALB2 mutations, in addition to germline BRCA1/2 mutation carriers.

https://www.practiceupdate.com/C/108866/56?elsca1=...

https://ascopubs.org/doi/10.1200/JCO.20.02151

DOI: 10.1200/JCO.20.02151 Journal of Clinical Oncology

{Free access to reporting and abstract. There appears to be a fee for access to the ASCO full article.}

Lumpie

Breast Cancer–Specific Mortality in Small-Sized Tumor With Stage IV Breast Cancer

October 28, 2020 The Oncologist

• This authors of this SEER database study evaluated breast cancer–specific mortality (BCSM) according to primary breast tumor size in over 5300 patients with metastatic breast cancer. Tumor size was not associated with BCSM. In patients with tumors <50 mm, the BCSM rate did not decline in association with decreasing tumor size. Among patients with triple-negative breast cancer, the BCSM rate was worst among patients in the T1a/T1bN2+ group.
• The authors hypothesize that T1a/T1b triple-negative breast cancers with regional lymph node metastases may be a surrogate for biologically aggressive disease.

https://www.practiceupdate.com/C/108609/56?elsca1=...

https://theoncologist.onlinelibrary.wiley.com/doi/...

https://doi.org/10.1002/onco.13567

{Free access to reporting and full article.}

Tinkerbell107

Re: Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination–Related Genes November 05, 2020 Journal of Clinical Oncology

This is disappointing news for ATM or CHEK2 mutations. No response to treatment. I was hoping to have Olaparib as a future treatment option. Although I'm glad to hear the drug helps others..

Lumpie

Tinkerbell107: I note that it was a small study - only 54 patients. I hope that maybe they will look at larger pools before relying too heavily on what seems like it should be starting point info. (Hope you have lots of options - and don't need any of them for a long time!)

ShetlandPony

Santabarbarian, re chronomodulation — I try to get the 13-hour overnight fast, and take my pills so they reach peak levels during the night when, I believe, cancer cells are more active.

Tinkerbell107

Lumpie: Thanks for the encouragement. Appreciate all your efforts in bringing forth the research studies.

arolsson

Hi lumpie and tinkerbell

just anecdotal evidence but after 7 lines of chemo and being told i was out of options I privately financed a foundation one test, found somatic PALB2 and was put on olaparib. my 11cm li ver tumor is at 5,6 after 3 months../amy

JoynerL

Thanks for all, Lumpie. So important. WOW, Arolsson, and good luck, Tinkerbell-that does sound like a small study.

Lumpie

arolsson: That is great news! Just goes to show... there is still so much we don't know. I know that a lot of us think that figuring out how to effectively personalize medicine is really important to so many people's effective treatment. We are all still lab rats... but in a good way, a way that contributes to health and future treatments, I hope.

BlueGirlRedState

(I also posted this on reducing dose, AIs) . Reducing dosage. Reading "The Cheating Cell" Athena Aktipis https://press.princeton.edu/books/hardcover/9780691163840/the-cheating-cell . She explores looking at cancer from an evolutionary view. Rather than trying to eradicate/kill cancer which might actually select for cells which resist treatment, she suggests "managing" the cancer which might select for cancer that is less prone to develop resistance. One approach is "adaptive therapy" where the cancer is kept at an "acceptable" size without too much harm/risk to the patient. She also suggests "faking" described in her book and here. the cancer https://chemoth.com/metronomic/adaptive-chemotherapy... This article suggests that while a nice idea, we are not there yet. https://www.oncozine.com/personalizing-cancer-treatment-why-adaptive-therapy-isnt-there-yet/ . In some sense, adaptive therapy makes sense, can we really expect to eradicate? At the same time I want it gone gone gone, not just "manageable". She also describes, briefly, how we are abe to successfully treat and eradicate some types of cancer. I wish and hope the same for breast cancer. She is an evolutionary biologist at Arizona State University.

theresa45

Tinkerbell107, I was on the small TBB Trial of Talzenna (another PARP inhibitor) for patients with BRACA-like mutations for almost a year. I have CHEK2 and FANCA germline mutations. The Olaparib Expanded trial evaluated similar BRACA-like mutations, and I was very sad when it did not show a response with many of the mutations (with exception of PALB2 and somatic BRACA1/2). However, as many have said, it was a very small trial. One on my friends who has a germline CHEK2 and somatic BRACA1 mutation responded well for a year on that trial, but was counted in the somatic BRACA mutation arm. I hope that further research will be done... I hope that women who might benefit from PARP inhibitors will have access to them. Despite my durable response to Talzenna, PARP inhibitors would probably not be recommended to me today...