Breaking Research News from sources other than Breastcancer.org
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New Standard for Metastatic HER2 Breast Cancer
Consistent PFS, OS benefit with combination including oral HER2 inhibitor tucatinib
Patients with heavily treated metastatic HER2-positive breast cancer lived significantly longer with the addition of an investigational anti-HER2 drug to trastuzumab (Herceptin) and chemotherapy, a large randomized trial showed.
Almost three times as many patients were alive without disease progression after 1 year when treated with tucatinib, trastuzumab, and capecitabine, as compared with the two drugs (33.1% vs 12.3%). The 2-year overall survival (OS) was 44.9% with tucatinib and 26.6% without it. Among patients with brain metastases, a fourth remained alive without disease progression at 1 year versus none of the patients randomized to placebo in addition to trastuzumab and capecitabine.
"Tucatinib in combination with trastuzumab and capecitabine has the potential to become a new standard of care in this population with and without brain metastases."
"Overall, tucatinib reduced risk of progression or death by 50%," Tierstein added. "I think this regimen may be considered a new standard of care for pretreated HER2-positive metastatic breast cancer. Very exciting."
San Antonio Breast Cancer Symposium
Source Reference: Murthy RK, et al "Tucatinib vs placebo, both combined with capecitabine and trastuzumab, for patients with pretreated HER2-positive metastatic breast cancer with and without brain metastases (HER2CLIMB)" SABCS 2019; Abstract GS1-01.New England Journal of Medicine
Source Reference: Murthy RK, et al "Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer" N Engl J Med 2019; DOI: 10.1056/NEJMoa1914609.
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Lumpie, said it before and do so again....you are a STAR! You’ve hopefully an idea now how much it helps the rest of us knowing there are people like you out there dedicated to sharing their knowledge.
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Thank you Karenfizedbo15!! You made my day!
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Chemo-Free Regimen Feasible in High-Risk Luminal Breast Cancer
Downstaging just as frequent with endocrine therapy plus CDK4/6 inhibitor
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Chemo-Free Regimen Feasible in High-Risk Luminal Breast Cancer
Downstaging just as frequent with endocrine therapy plus CDK4/6 inhibitor
A neoadjuvant chemo-free combination achieved similar responses to a standard chemotherapeutic regimen for postmenopausal women with high-risk luminal B breast cancer, a small randomized trial out of Spain indicated.
In the CORALLEEN trial, 46.9% of patients treated with the aromatase inhibitor letrozole (Femara) plus CDK4/6 inhibitor ribociclib (Kisqali) achieved a low risk of relapse (ROR) following surgery, as compared with 46.1% in the chemotherapy group...
"Neoadjuvant ribociclib and letrozole in high-risk luminal B breast cancer achieves high rates of ROR-low disease at surgery," said Gavilá during an oral abstract session here.
While Gavilá explained that chemotherapy does this just as well, and is the current standard treatment, it comes at the price of higher rates of toxicity.
a chemo-free treatment strategy based on CDK4/6 inhibition is worth exploring in future neoadjuvant trials,"
The Lancet Oncology
Source Reference: Prat A, et al "Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2-negative, luminal B breast cancer (CORALLEEN): An open-label, multicentre, randomised, phase 2 trial" Lancet Oncol 2019; DOI: 10.1016/S1470-2045(19)30786-7.Secondary SourceThe Lancet Oncology
Source Reference: Cristofanilli M, et al "Time for a shift in molecular down staging in luminal breast cancer" Lancet Oncol 2019; DOI: 10.1016/S1470-2045(19)30806-X.
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Residual Cancer Burden Predicts Patient Outcomes Across Breast Cancer Subtypes
Residual cancer burden (RCB) after neoadjuvant chemotherapy has been shown to be an accurate long-term predictor of disease recurrence and survival across all breast cancer subtypes, according to data from a large meta-analysis presented at the 2019 San Antonio Breast Cancer Symposium.
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T-DM1 for Early Stage Breast Cancer
Promising efficacy but higher discontinuation rates and cost likely a deterrent
Adjuvant treatment with ado-trastuzumab emtansine (Kadcyla), or T-DM1, demonstrated acceptable efficacy as a standalone treatment for women with stage I HER2-positive breast cancer, but failed to reduce clinically relevant toxicities, a randomized phase II trial found.
The so-called ATEMPT study met its primary efficacy endpoint, with 97.7% of patients treated with T-DM1 remaining disease free at 3 years (95% CI 96.2%-99.3%), Sara Tolaney, MD, MPH, of the Dana-Farber Cancer Institute in Boston, reported here at the San Antonio Breast Cancer Symposium (SABCS).
...the rate of clinically relevant toxicities -- the study's other primary endpoint -- was no better than standard paclitaxel plus trastuzumab (TH), landing at 46% for both arms.
grade ≥3 non-hematologic events were similar between the T-DM1 and TH arms (10% vs 11%, respectively), as were rates of febrile neutropenia (0% vs 2%) and grade ≥4 hematologic events (1% vs 0%).
"It's also important to note that not all toxicities that are significant for our patients are captured in this clinically relevant toxicity endpoint, such as alopecia,"
"Given the low event rate seen in this trial, T-DM1 may be considered an alternative treatment approach to TH for select patients with stage I HER2-positive disease..." {but} "For stage I disease, paclitaxel and trastuzumab remains the standard of care."
Primary Source
San Antonio Breast Cancer Symposium
{Gratuitous editorial commentary: toxicities were similar (curious given that I think neutropenia is much more common on taxanes); not having (sometimes permanent) alopecia is a BIG deal!; the article discusses at some length the cost of Tx with Kadcyla. The bills I have seen would indicate that Kadcyla is less expensive than T&H, certainly less than TCHP. I would be interested to hear from others about billed costs of these drugs.}
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HRT Has 20-Year Impact on Breast Cancer Risks
Prospective data confirm long-term benefit with estrogen-only and harm with added progestin
Menopausal hormone replacement therapy (HRT) with estrogen alone yielded lasting reductions in breast cancer incidence and death while estrogen plus progestin showed persistent increases in both, long-term data from two Women's Health Initiative (WHI) trials indicated.
At over 16 years of cumulative follow-up, women with prior hysterectomy randomized to estrogen-only HRT had a 23% reduction in breast cancer diagnosis compared to those assigned placebo (HR 0.77, 95% CI 0.62-0.92), driven in large part by fewer diagnoses of estrogen receptor-positive/progesterone receptor-negative disease,
Primary Source
San Antonio Breast Cancer Symposium
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Subdivision of M1 Stage for De Novo Metastatic Breast Cancer to Better Predict Prognosis and Response to Primary Tumor Surgery
Patients with de novo metastatic breast cancer (MBC) constitute a heterogeneous group with different clinicopathologic characteristics and survival outcomes. Despite controversy regarding its prognostic value, primary tumor surgery may improve survival for selected patients.
Subdivision of M1 stage facilitates prognosis prediction and treatment planning for patients with de novo MBC. Treatment offered should be decided in a coordinated multidisciplinary setting. Primary tumor surgery may play an important role in the management of selected patients.
DOI: https://doi.org/10.6004/jnccn.2019.73320 -
Checkpoints Show Different Outcomes in Breast Cancer
Atezolizumab misses complete response benefit in triple negative patients
The PD-L1 checkpoint inhibitor atezolizumab (Tecentriq) plus chemotherapy came up short in getting women with early stage triple-negative breast cancer to a pathologic complete response in the neoadjuvant setting when compared with chemotherapy alone, researchers reported...
In the preliminary results of the NeoTRIPaPDL1 Michelangelo trial, 43.5% of patients achieved a pathologic complete response when they were taking atezolizumab and the chemotherapy regimen of carboplatin and nab-paclitaxel compared with 40.8% of those taking only the chemotherapy (P=0.66)
patients who had PD-L1 positive tumors fared better with atezolizumab therapy than women who had PD-L1 negative tumors. Women with a high level of PD-L1 were twice as likely to achieve a pathologic complete response if they were in the atezolizumab group of patients.
In the KEYNOTE-522 trial ...64.8% of the triple-negative breast cancer patients achieved pathologic complete response with pembrolizumab plus two chemotherapy regimens compared with 51.2% of patients treated with chemotherapy alone.
...atezolizumab appeared to show activity in the metastatic setting, and was surprised that it did not show similar activity in the early stage setting.
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Yikes with the RCB study. I mean, I knew at some level, but this did not start my day off well...
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I am in the same boat Lexica and I agree...BUMMER
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Lumpie I can answer your question about the cost of those drugs. My Kadcyla is being billed at $8050 every 3 weeks. My Herceptin was $6300 and Perjeta was $5625 earlier this year (it went up again this year), again every 3 weeks. Taxol is cheap and was only a couple hundred dollars when every 3 weeks ($300-$400). Taxol and Herceptin without Perjeta would be cheaper than Kadcyla, but THP is more expensive. A large percentage drop the Perjeta due to side effects, and a lot of early stage never even go on Perjeta, they just do the one year of Herceptin. So it's valid to compare the cost of Kadcyla to TH like they did in the study, and from my billing rates Kadcyla would definitely be more expensive.
What I don't understand is why they would have someone who is early stage do one full year of chemo instead of one year of a biologic with relatively few side effects like Herceptin.
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LoriCA,
Wow! Thanks for sharing that info. Where are you getting your drugs!? My were being billed at:
Herceptin $9,424 discounted to $8,010 per dose
Perjeta $12,180 discounted to $10,353 per dose
That was in April. I wonder if it went up after that? Yikes! I do not see the bills for my Kadcyla since I am in a clinical trial.
I know that my Taxotere was being billed at around $3,500 per dose. I also got Cyclophosphomide. Can't find cost records for it right now. (All of these are drug only prices. Does not include administration, etc.)
I was actually told by one woman that she was being bill approximately triple the amount I was. Insane.
The combination of drugs used and these very different price numbers would make a big difference in the total treatment cost for early stage. Based on the charges for my TCH vs your Kadcyla, the Kadcyla would be cheaper. As I noted, one huge advantage of Kadcyla would be avoiding hair loss. I realize that cost analysts may say "not a big deal" but for those of us that 1) live with the loss and 2) *never* get our hair back, it is a HUGE, HUGE deal. Not to mention the fact that I am tolerating Kadcyla so, so much better than TCH. I don't feel nearly as bad as on the taxane. Huge QOL issue for me.
PS: Does it not strike people as utterly crazy that we are all charged incredibly different prices for these drugs? Crazy-making!
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Lumpie I'm not sure if some of the drugs are dosed based on weight, but I'm a petite 5'4" so maybe that affects my costs. I live in one of the most expensive areas of the country (LA metro) and everything is more expensive here, so I don't understand why someone in another part of the country would pay more. Unless maybe the volume of patients treated in an area like mine means the facilities get volume discounts on drugs hahaha! It is crazy that pricing could be so different for each of us. Someone once posted that their cost for H&P was $21,000 every 3 months and it left me scratching my head, how could that be? (And yes, the costs I posted were for drugs only.)
I agree about no hair loss and better QoL than a taxane. That's the reason I asked to move on to Kadcyla this time instead of trying another Herceptin + chemo combo. I wanted to keep my hair for Christmas this year haha! But still, a full year of chemo vs a few months when you're early stage is something to think about. QoL of Herceptin for one year is much better than QoL of Kadcyla, especially if they're like me and have a tough time getting along with Kadcyla. It says there is a higher discontinuation rate for Kadcyla than TH, and I'm guessing that's due to the SEs. I think Kadcyla would have to show a major improvement over TH to be worthwhile. And a small number of people do lose their hair with Kadcyla for some reason (3.9% according to manufacturer), so it's not a complete guarantee one wouldn't lose their hair.
Would be interesting to hear what early stage people think about it.
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Thanks Murfy. Very interesting research about LE.
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Denosumab Does Not Alter the Course of Early Breast Cancer
-D-CARE trial failure spurs reassessment of adjuvant treatment with bone-modifying agent
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I don’t remember seeing this posted here yet. Sorry if I am reposting.
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Radiotherapy for ductal in situ carcinoma ups mortality risk in invasive second breast cancer
For women with primary ductal carcinoma in situ (DCIS), use of radiotherapy (RT) is associated with increased rates of breast cancer-specific mortality for those women who subsequently develop an invasive second breast cancer (SBC), according to a study published in the November issue of the Journal of the National Comprehensive Cancer Network...
The researchers found that even after controlling for cancer stage, prior RT was associated with higher rates of breast cancer-specific mortality (hazard ratio, 1.70; 95 percent confidence interval, 1.18 to 2.45; P = 0.005). The risk trended higher in patients with ipsilateral versus contralateral SBC (hazard ratio, 2.07 versus 1.26; P = 0.16). Patients with ipsilateral SBC were younger and more often lacked estrogen receptor expression compared with patients who developed contralateral SBC...
https://medicalxpress.com/news/2019-12-radiotherapy-ductal-situ-carcinoma-ups.html
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I feel like that article is misleading. It should be comparing survival in women who get radiotherapy after DCIS vs women who don't, with both groups randomly assigned. It could be that women who have radiotherapy and go on to develop a second breast cancer had a radiation-resistant strain of breast cancer to begin with, which is more aggressive and less treatable. Whereas the women who didn't have radiotherapy may have developed a second breast cancer more often, and many of theirs were successfully treated with radiotherapy, but just as many died of radiation-resistant breast cancer in the end. Not to mention, some of those women could have been recommended radiation because their DCIS was of a more aggressive variety and thus more likely to recur.
Edit: I tracked down the original article, and it does cover this possibility:
"One factor likely contributing to the finding of increased mortality associated with ipsilateral SBC after prior RT is that prior radiation to the ipsilateral breast limits subsequent salvage options in the same breast. In our cohort, the proportion of patients receiving RT for contralateral SBC was higher than the proportion receiving RT for ipsilateral SBC after DCIS (P<.001). Another hypothesis that may explain this finding is that BCS followed by RT is less effective in preventing recurrence of invasive disease that is more aggressive biologically, and therefore prior treatment with RT may in fact confer a worse prognosis among patients who develop an invasive SBC. Indeed, our findings showed that patients who developed ipsilateral SBC were younger at the time of SBC development and had breast cancers that were more likely to lack ER expression, characteristics that are associated with more aggressive cancer biology. These possible explanations for the increased mortality associated with prior RT are not mutually exclusive, and both may be true."
Full article for anyone who is interested: https://jnccn.org/view/journals/jnccn/17/11/article-p1367.xml
In any event, looking only women at who have gotten a second breast cancer for the study instead of comparing all women and seeing how many of them 1) got second breast cancers and 2) survived completely discounts all the women who were cured by the radiation they received. If you did a study the other way around, discounting all the women who died or had recurrence and looking at the effects of treatment in the remaining population, it would be totally ridiculous.
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hapa, thats exactly the thought that occurred to me. Thanks for stating it so well.
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A Genetic Test Led Seven Women in One Family to Have Major Surgery. Then the Odds Changed.
Two sisters, their mother and aunts showed a mutation on a BRCA gene and an elevated risk of breast and ovarian cancer. But these interpretations can be revised.
Read in The Wall Street Journal: https://apple.news/Ap2sanVeJRkatMHZ2NLBF-Q
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marijen, I read this article in the WSJ yesterday, and just read again the comments from readers.
It's disheartening, in so many ways.
The family involved seems to have not understood that genetic information is ever-changing - this should have been clearly explained to them by a genetic counsellor, as it was explained to me 14 years ago.
The articles notes "There are tens of thousands of BRCA variants and new research reveals that not all confer the same level of risk to a patient. Some gene variants “have intermediate or moderate levels of risk, not full-blown risk," says Fergus J. Couch, a professor at the Mayo Clinic, whose lab has worked on some of these studies.". Seriously, this is being presented as new news? I knew this from my own reading 14 years ago prior to my discussions with the genetic counsellor, and this was confirmed in that discussion. Anything I've read that mentions risk levels associated with the BRCA1 and BRCA2 mutations always presents a range of risk, never a single number.
The way the family feels now, and the way the story has been presented, indicates that some or all of the women regret their decisions to have prophylactic surgeries, based on the new information about their BRCA mutation. Well, what about the fact that they still have the family history of cancer? That hasn't changed. And it's not well explained that the new VUS status for their particular BRCA mutation does not mean that this mutation might not in fact present a high risk - VUS means that maybe it will or maybe it won't, and we just don't know yet. That's covered off in the article in one short sentence that's easy to miss. I appreciate that the family members are angry because they had these surgeries thinking their risk was much higher - but they are still high risk. And with their family representing such a large percent of the people with this mutation, and with so many of them having had prophylactic surgeries, at this point it may be very difficult to ever truly know what their risk really was.
It's mentioned in the article, but not emphasized, that changing the assessment of a genetic mutation from high risk to VUS status happens to only 1% of genetic mutations. So this cautionary tale about a very rare situation will scare some people away from genetic testing; not knowing their positive status and taking preventative action might lead to some deaths from cancers that could have been averted.
Then there are the letters. So little understanding of why people get genetic testing and why those who test positive for a high risk mutation often choose prophylactic surgery. No understanding that screening can miss some breast cancers and that even with extensive monitoring, sometimes breast cancers are not found when they are early stage, or that sometimes early stage breast cancer kills. One writer mentioned a 100% survival rate for breast cancer caught early and no one has contradicted her and provided the facts. A few people, all personally affected, have mentioned that there is no effective way to screen for ovarian cancer and that most ovarian cancers are found at Stage III or IV, but no one unaffected seemed to have any idea about this. One man mentioned that he is BRCA positive and has had breast cancer but every other writer seems to think this is a female issue.
I know how poorly educated the general public is about the realities of breast cancer so the fact that they are even more ignorant about genetic testing and the implications of being positive shouldn't surprise me, but it is demoralizing.
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This may have been posted before since it was in the news earlier this year, but I am just seeing it now, so thought I'd share.
Gain Fat—Lose Metastasis: Converting Invasive Breast Cancer Cells into Adipocytes Inhibits Cancer Metastasis
"Adipogenesis-inducing drug combinations repress metastasis in preclinical models"
"Delineation of the molecular pathways underlying such trans-differentiation has motivated a combination therapy with MEK inhibitors and the anti-diabetic drug Rosiglitazone in various mouse models of murine and human breast cancer in vivo. "
https://www.cell.com/cancer-cell/fulltext/S1535-6108(18)30573-7
Here is an easier - to -read article about the research:
"Scientists Successfully Turn Breast Cancer Cells Into Fat to Stop Them From Spreading"
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New Standard Likely for Some Metastatic HER2 Breast Cancer
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Study by Geisel group details process enzyme plays in cancer
Using cell models in the lab, the team found that LPL [Lipoprotein Lipase] docks on the surface of breast cancer cells, enabling them to absorb whole fat particles from the bloodstream...
Pinning down how cancer cells get the fat they need to replicate is important, Kolonin said, because patients need to know what effect their diet may have on their cancer risk or progression of their existing disease.
In an effort to reduce their consumption of carbohydrates and sugar — which cancer cells may use to make fat — some patients have turned to the high-fat, adequate-protein ketogenic diet, Kolonin said.
But if the Geisel researchers' findings are borne out in future studies, "reducing fatty acids in diet is something to consider," he said.
Then the question left for researchers is between carbohydrates and fat: "What's the worse of the two evils?" Kolonin said.
https://www.vnews.com/Dartmouth-researchers-find-breast-cancer-cells-gobble-up-dietary-fat-31464521
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CytoDyn Reports Early, But Strong Positive Clinical Responses for Two Patients, One in Metastatic Breast Cancer and One in Metastatic Triple-Negative Breast Cancer Trials
CytoDyn... a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced today continued promising clinical responses from its metastatic triple-negative breast (mTNBC) Phase1b/2 trial and its trial investigating leronlimab for the treatment of metastatic breast cancer (MBC).
"In the first patient, we're encouraged to see that after 11 weeks these additional data provide further preliminary evidence of efficacy, as demonstrated by sustained undetectable levels of CTCs and a reduction of cancer-associated macrophage like cells (CAMLs)," said Bruce Patterson, M.D., Chief Executive Officer of IncellDx...
CytoDyn's second patient enrolled is a stage 4 MBC patient. The metastasis progressed to the liver, lung and brain... This patient received her first injection of leronlimab on November 25, with one 700 mg dose each week... "The results from two subsequent scans of the metastatic lesions for this second patient demonstrated shrinkage of the tumors at both timepoints following the first leronlimab injection, reduction in brain edema, and remarkably, disappearance of several metastatic tumors."
The U.S. Food and Drug Administration (FDA) has granted a "Fast Track" designation to CytoDyn for two potential indications of leronlimab for deadly diseases. The first as a combination therapy with HAART for HIV-infected patients and the second is for metastatic triple-negative breast cancer (mTNBC). Leronlimab is an investigational humanized IgG4 mAb that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases, and other diseases including NASH...
In the setting of cancer, research has shown that CCR5 plays an important role in tumor invasion and metastasis. Increased CCR5 expression is an indicator of disease status in several cancers. Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 98 percent in a murine xenograft model. CytoDyn is therefore conducting a Phase 2 human clinical trial in metastatic triple-negative breast cancer and was granted Fast Track designation in May 2019.
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