SABCS: Go Low With Tamoxifen for Ductal Carcinoma

Daily use of low-dose (5 mg) tamoxifen (multiple brands) for a shorter-than-usual treatment period (3 years) for patients with ductal carcinoma in situ (DCIS) and other forms of noninvasive breast cancer halved the recurrence of new breast cancer events in comparison with placebo, a new Italian study indicates.

Noninvasive breast cancers are also known as breast intraepithelial neoplasias. Other types, in addition to DCIS, that were included in the randomized, phase 3 TAM-01 clinical trial were lobular carcinoma in situ (LCIS) and atypical ductal hyperplasia (ADH).

Tamoxifen is typically prescribed post surgery at a dosage of 20 mg/day for 5 years for DCIS and these other conditions, said lead study author Andrea De Censi, MD, of the National Hospital EO Ospedali Galliera – SC Oncologia Medica in Genoa, Italy.

Tamoxifen was developed in the 1960s, but the minimal effective dose has never been established, he said during a press briefing here at San Antonio Breast Cancer Symposium (SABCS) 2018, where the study was presented.

De Censi and colleagues hypothesized that a reduced dose and a shorter duration would be effective. That idea was based on a 2003 study from this same Italian group, which showed that 5 mg of tamoxifen was comparable to 20 mg in reducing breast cancer proliferation, as measured by Ki-67 level.

In the new 500-patient trial, 5.5% patients in the low-dose tamoxifen arm (n = 14 of 253) had either experienced disesase recurrence or had new disease, including invasive disease, compared with 11.3% in the placebo arm (n = 28 of 247).

Median follow-up was 5.1 years.

With the low dose, rates of occurrence of two worrisome side effects of tamoxifen — endometrial cancer (which is rare), and deep vein thrombosis (DVT)/pulmonary embolism (PE) — were not different from the rate seen among the patients taking placebo, reported De Censi. Menopausal symptoms, the other common side effect, were not worsened, with the exception of hot flashes, in which the drug had a borderline effect.

Prescribing low-dose tamoxifen involves a twist, De Censi explained. A 5-mg pill is not currently available, so patients need to take a 10-mg pill every other day.

In a press statement at the meeting, De Censi said that the new results are “practice changing.”

“Tamoxifen 10 mg every other day is applicable in practice [starting] from tomorrow,” he told reporters.

Virginia Kaklamani, MD, of UT Health San Antonio, embraced the idea. She is a codirector of the SABCS and acted as press briefing moderator.

“Looking at these data, especially for the ADH and LCIS patients, I would definitely give lower doses of tamoxifen,” she said, explaining that the data were most compelling for those two groups.

She added: “If I have a DCIS patient who is not tolerating tamoxifen at the 20-mg dose, I would be extremely happy to lower it to 5 mg based on these data.”

But will patients take the drug? Tamoxifen has a reputation among patients, said Marissa Weiss, MD, a Philadelphia-based radiation oncologist and head of breastcancer.org, a consumer website, who attended the press conference.

Patients have heard too many of the “bad stories” and not enough of the good ones, commented Weiss. “For people to be receptive to this, we almost need to reintroduce it as a new medicine,” she said.

For reasons not illuminated by the study, treatment adherence was not high. A total of 64.8% of patients in the tamoxifen arm and 60.7% of patients in the placebo arm did not adhere to the regimen.

More About Adverse Events

De Censi also reported that there were no statistically significant differences between the two arms for an array of menopausal symptoms, such as hot flashes, vaginal dryness, and pain during intercourse.

There were 12 serious adverse events in the low-dose-tamoxifen arm and 16 in the placebo arm.

SERIOUS AES	TAMOXIFEN	PLACEBO
Endometrial cancer	1	0
DVT or PE	1	1
Other neoplasms	4	6
Heart disease	2	2
Other	3	5
Death	1	2
Total	12	16

“When we compare our low-dose tamoxifen data with results from the NSABP B-24 and NSABP-P1 trials of tamoxifen given at 20 mg per day, we see comparable risk reduction and significantly reduced serious adverse events, respectively,” said De Censi in a press statement at the meeting.

The study was supported by the Italian Ministry of Health, the Italian Association for Cancer Research, and the Italian League Against Cancer. Dr De Censi has financial ties with Indena SpA, Roche, Pfizer, Janssen, Novartis, Sanofi-Aventis, Quintiles, Gilead, and MacroGenics. Dr Kaklamani has disclosed no relevant financial relationships.

https://www.medscape.com/viewarticle/906170#vp_1

Gene that allows you eat as much as you want could help combat obesity

It sounds too good to be true, but a novel approach that might allow you to eat as much food as you want without gaining weight could be a reality in the near future.

When a single gene known as RCAN1 was removed in mice and they were fed a high fat diet, they failed to gain weight, even after gorging on high fat foods for prolonged periods.

The international team behind the study are hopeful a similar approach that inhibits this gene will also be effective with humans to combat obesity and serious diseases like diabetes.

Led by Professor Damien Keating at Flinders University, the study used a huge genetic screen in rodents to identify novel genetic candidates that may cause obesity, potentially paving the way for new drug therapies.

“We know a lot of people struggle to lose weight or even control their weight for a number of different reasons. The findings in this study could mean developing a pill which would target the function of RCAN1 and may result in weight loss,” Professor Keating says.

Obesity is a major global health epidemic, resulting in increased risk of serious diseases like type 2 diabetes, and heart disease, but avenues for effective therapeutic treatments are lacking.

There are two types of fat in the human body- brown fat burns energy, while white fat stores energy.

Professor Keating says blocking RCAN1 helps to transform unhealthy white fat into healthy brown fat, presenting a potential treatment method in the fight against obesity.

“We have already developed a series of drugs that target the protein that this gene makes, and we are now in the process of testing them to see if they inhibit RCAN1 and whether they might represent potential new anti-obesity drugs,”

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“In light of our results, the drugs we are developing to target RCAN1 would burn more calories while people are resting. It means the body would store less fat without the need for a person to reduce food consumption or exercise more.”

Two thirds of Australian adults and a quarter of children are either overweight or obese, and the statistics are just as concerning in Britain and the US.

“We looked at a variety of different diets with various timespans from eight weeks up to six months, and in every case we saw health improvements in the absence of the RCAN1 gene.”

The researchers say these findings open up a potentially simple treatment but further studies are required to determine if they translate the same results to humans.

“Our research is focused on understanding how cells send signals to each other and how this impacts health and the spread of disease”.

“We really want to pursue this, it’s exciting and we have research funding from the Australian government through the National Health and Medical Research Council to continue to explore viable options. These results show we can potentially make a real difference in the fight again obesity.”

Source:

https://www.flinders.edu.au/

https://www.news-medical.net/news/20181204/Gene-that-allows-you-eat-as-much-as-you-want-could-help-combat-obesity.aspx

High CTC Count Favors Chemo in First-Line ER+, HER2- Metastatic Breast Cancer

Higher circulating tumor cell (CTC) level is associated with a better response to chemotherapy compared with endocrine therapy, according to data from the STIC CTC trial presented at the 2018 San Antonio Breast Cancer Symposium in San Antonio, Texas.¹

There is currently no predictive biomarker to aid the decision of whether to treat with chemotherapy or hormone therapy for patients with estrogen receptor (ER)-positive metastatic breast cancer. CTC count has previously been established as a strong prognostic marker in this population. The purpose of this study was to evaluate CTC count using the tool CellSearch.

The multicenter, phase 3, noninferiority STIC CTC trial enrolled 778 patients with hormone receptor-positive, HER2-negative metastatic breast cancer to receive first-line treatment with chemotherapy or endocrine therapy. The choice of treatment was by random assignment, selected by clinically-driven choice or CTC-driven choice (CTC count not disclosed, HT or CT administered as decided a priori). In the CTC count arm, patients with low CTC levels (as defined as < 5 CTC/7.5 mL) received endocrine therapy, whereas patients with high CTC levels (as defined as ≥ 5 CTC/7.5 mL) received chemotherapy.

The primary end point was progression-free survival (PFS) and the secondary end points included overall survival (OS) and prespecified subgroup analyses.

The CTC count was noninferior to the clinician’s choice arms for PFS, with a median of 15.6 months (95% confidence interval [CI], 12.8-17.3) compared with 14.0 months (95% CI, 12.2-16.0) in the clinician’s choice arm (hazard ratio [HR], 0.92; 90% CI, 0.80-1.06), based on the prespecified noninferiority margin of 1.25.

OS was similar between arms, with a 2-year rate of 82.1% in the CTC count arm compared with 81.4% in the clinician’s choice arm.

CTC count confirmed clinician’s choice in 67% of patients who received endocrine therapy and 48% of patients who received chemotherapy. For discordant cases, CTC count that differed from clinician’s choice resulted in a switch in therapy. In these cases, patients who were switched to chemotherapy demonstrated a significantly prolonged PFS compared with endocrine therapy (median, 15.5 months vs 10.5 months). There was a trend toward improved OS with chemotherapy versus endocrine therapy based on CTC count (median, 42.0 vs 37.1 months). Patients who were switched to endocrine therapy based on low CTC count demonstrated no difference in PFS between arms.

The authors concluded that high CTC count favors chemotherapy compared with endocrine therapy. As a result, the authors stated in a press release that, “CTC count should be included in the decision algorithm for HR-positive, HER2-negative metastatic breast cancer patients.”²

References

1. Bidard FC, Jacot W, Dureau S, et al. Clinical utility of circulating tumor cells (CTC) count to choose between 1^stline hormone therapy & chemotherapy in ER+ HER2- metastatic breast cancer. Presented at: 2018 San Antonio Breast Cancer Symposium; San Antonio, TX: December 4-8, 2018. Abstract GS3-07.
2. Cavallo J. Circulating Tumor Cell Count Could Help Choose Treatment for Metastatic Breast Cancer Patients. 2018 SABCS press release. http://www.ascopost.com/News/59547. Published December 6, 2018. Accessed December 6, 2018.

https://www.cancertherapyadvisor.com/sabcs-2018/high-ctc-count-favors-chemotherapy-first-line-er-her2-metastatic-breast-cancer/article/819551/

SABCS: Axillary Radiotherapy as Good as Surgery in Breast Cancer

The 10-year follow-up of the controversial AMAROS study appeared to confirm that irradiating the axilla after a positive sentinel node diagnosis is as good in preventing breast cancer recurrence as lymph node dissection, and reduced the risk of lymphedema by 50%, researchers reported here.

After 10 years, 7 of 744 women who underwent lymph node dissection experienced a recurrence in the axilla compared with 11 of 681 women who underwent radiotherapy (P=0.37), according to Emiel Rutgers, MD, PhD, of the Netherlands Cancer Institute in Amsterdam.

At a press conference at the annual San Antonio Breast Cancer Symposium (SABCS), Rutgers said that the rate of overall survival at 10 years was similar between the two groups (84.6% with surgery vs 81.4% with radiotherapy, P=0.26).

What was different between the groups, he noted, was the debilitating adverse event of lymphedema. Among women who had surgery, 31.4% were diagnosed with lymphedema after 1 year compared with 16.1% of the women who had radiotherapy.

At 3 years, 21.8% of women who had surgery complained of lymphedema compared with 11% of women who had radiotherapy. And at 5 years, these rates were 18.2% and 6.6%, respectively.

“Both lymph node dissection and radiotherapy to the axilla provide excellent and comparable locoregional control in sentinel node positive breast cancer patients after 10 years,” Rutgers said. “There is significantly less lymphedema after radiotherapy after 5 years. Axillary radiation therapy can be considered standard procedure.”

For the study, the researchers enrolled women who had been diagnosed with T1-T2 breast cancer and were going to undergo sentinel node biopsy. Patients had no clinical evidence of local spread of disease to the axillary lymph.

“Traditionally, those patients who had cancer detected in a sentinel lymph node biopsy underwent axillary lymph node dissection, which is an effective but invasive surgical procedure that is associated with adverse side effects such as lymphedema and difficulties moving the arm,” he said.

The researchers assigned 598 women to undergo the surgical procedure if the sentinel node biopsy proved positive and 535 women to receive radiation therapy instead.

Rutgers told MedPage Today that about 10% of each group opted out of their assigned study arm when their sentinel node biopsy results became known.

He said that 5 years ago when the results were similar, the uptake among the medical community for radiotherapy for these patients was not rapid; hence, the 10-year follow-up was completed in hopes of bolstering the case for radiation. While accepted in the Netherlands, there is still reluctance to only perform radiation in Europe and North America for women with positive sentinel nodes.

In commenting on the study, SABCS press conference moderator Virginia Kaklamani, MD, of the University of Texas Health San Antonio, told MedPage Today, “When you have a positive lymph node, intuitively you want to clear this disease, and in this study one-third of the women who had a positive sentinel node also had positive lymph nodes — yet they did not benefit from surgery over radiation.”

“That leads us to believe that we can de-escalate therapy, and we can offer radiation instead of axillary dissection,” Kaklamani added. She said that after 5 years the results were questioned due to a short period of follow-up.

“But with this study, out to 10 years, I think we can be confident of these results,” she said. “The benefit of de-escalating therapy is that you are helping the patients have a better quality of life by decreasing the morbidity of the treatment. With axillary dissection, patients have a higher probability of lymphedema — as high as 30%, whereas with radiation, that risk is now 14% to 15%, cutting the risk by half.”

Rutgers and Kaklamani disclosed no relevant relationships with industry.

• Primary Source

  San Antonio Breast Cancer Symposium

  Source Reference: Rutgers E, et al “Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: 10 year follow up results of the EORTC AMAROS trial (EORTC 10981/22023),” SABCS 2018; Abstract GS4-01.

https://www.medpagetoday.com/meetingcoverage/sabcs/76777

Smart tattoos turn your skin into a health tracker

Harvard University

There’s a common problem with health-tracking devices like smartwatches: they’re not really attached to you, which leaves you relying on a short-lived battery and a wireless connection. Even a self-powered patch has its limits. That’s where Harvard and MIT think they can help: they’ve developed smart tattoos that effectively place health sensors in your skin, no power or wireless link required. The ink in the tattoos reacts to the chemical composition of your interstitial fluid, which reflects the state of your blood. A green ink grows more intense to let athletes know when they’re dehydrated, while another green ink turns brown to warn diabetics when their glucose levels go up.

And unlike that tattoo you got on a wild night in college, you’re not stuck with it. With enough refinement, the scientists expect to make tattoos that only last for as long as you need them. They could be invisible unless subjected to certain kinds of light, too, so you wouldn’t have to explain your ink to your friends. if you weren’t sure what the symbols on your arm meant, a smartphone app could analyze them to tell you exactly how you’re doing.

It could be a long while before you’re sporting tattoos that are as informative as they are decorative. The project is as much about inspiring “potential” among both artists and scientists, as well as to address ethical questions. If your tattoo is visible, are you comfortable with the idea of everyone seeing your blood sugar level the moment you put on a short-sleeved shirt? Look at it this way, though: if you’re tired of strapping devices to your arms or wrists just to quantify your health, this could be much more comfortable.

Source: Harvard Gazette, ACM

https://www.engadget.com/2017/10/01/smart-tattoos/

How Donald Trump Is Radically Reforming Obamacare

In the face of congressional inaction, the Trump administration has set out to reform Obamacare by executive order. The reforms stretch the boundaries of what many thought was possible without an act of Congress. Although some changes are still in the comment period (before the rules become formalized), the Trump reforms in some ways are more radical than Obamacare itself.

Personal and portable health insurance. The United States has a long history of encouraging health insurance at the place of work. Premiums paid by employers avoid federal and state income taxes as well as the Social Security (FICA) payroll tax. By contrast, unless they get Obamacare subsidies, most Americans receive no tax relief if they buy health insurance on their own.

Unfortunately, group insurance is not portable. When people leave their job, many must turn to individually purchased health insurance instead. This is the primary source of the “pre-existing condition” problem. Before Obamacare, insurers in the individual market could and did deny coverage to people with expensive health conditions, although Wharton health economist Mark Pauly finds that the instances of this were rare.

So why not let employees have insurance they can take with them from job to job and in and out of the labor market? This idea is highly popular in public opinion polls. But under the Obama administration, employers who did this could be fined as much as $100 per employee per day, or $36,500 per employee per year – the largest fine in all of Obamacare.

The Trump administration is proposing to get rid of those fines and actually encourage the purchase of individually owned insurance, using employer funds, through something called a Health Reimbursement Arrangement (HRA). Small businesses are allowed to do this as a result of the 21^st Century Cures Act, passed in 2016. Trump is now proposing to allow employers of any size the same opportunity.

Given the sorry state of the individual market in most places, why would employers and their employees find this option attractive? Because of other Trump reforms.

In addition to broadening the scope for Association Health Plans earlier in the year, the administration announced last Thursday that  states will have the ability to (1) create risk pools and/or risk reinsurance in order to bring down premiums for average buyers, (2) create defined contribution accounts (combining Obamacare subsidies with other money) from which families can select health insurance that better meets their needs, (3) use Obamacare money to create a new and different system of subsidies and (4) create new insurance options, including non-qualified health plans.

Then on Monday, that administration released Reforming America’s Healthcare System Through Choice and Competition. This is the first time any administration has explicitly acknowledged that the most serious problems in health care arise not because of market failure, but because of unwise government policies; and it is the first time the federal government has committed to the idea of liberating the medical marketplace. In many ways the document is very similar to ideas I first proposed in Regulation of Medical Care: Is the Price Too High? (Cato: 1980)

I’ll have more to say about these policy changes in future posts.

The Treasury department believes as many as 10 million people will obtain individually owned insurance through their employers under the new rules. Harvard Business School’s Regina Herzlinger thinks the number could be much higher than that.

Tax fairness. The latest Trump executive order goes a long way toward eliminating unfairness in the tax code. For example, an above-average-income family would be able to obtain individually owned insurance with the same tax advantages as group insurance.

Below-average-income families have the opposite problem. Since these families pay no income taxes, their only tax subsidy at work is the avoidance of the payroll tax. This is well below the subsidies available in the Obamacare exchanges. Going forward, these families will be able to use employer money to obtain subsidized insurance in the exchanges. (But there will be no double dipping – it’s one subsidy or the other.)

A flexible savings account. More than 30 million Americans have a Health Savings Account, allowing them to manage some of their own health care dollars. These accounts are rigidly constrained, however. Because of an across-the-board high deductible and other requirements, most health plans sold in the Obamacare exchanges are not HSA-compatible.

HRAs, by contrast, can wrap around any health insurance plan and are available to pay for expenses insurance doesn’t pay for. Employer deposits to HRAs would give employees access to the full range of products available on the individual market. Money not spent on premiums would be available to pay other expenses, including deductibles and copayments.

Insurance tailored to family needs. Obamacare tries to force low-income families to buy the wrong kind of insurance. If a low-income couple has the misfortune to have a million-dollar premature baby, Obamacare insurance will pay the hospital the million dollars. But under some plans, the couple must pay the first $7,000 of medical expenses out of their own pocket. That’s great for hospitals, but it does almost nothing to help the family.

Before there was Obamacare, fast food workers often had limited benefit insurance – paying, say, the first $25,000 or $50,000 of medical expenses. This kind of insurance gave them easy entry into the health care system, although the cost of rare, catastrophic events was shifted to others.

Fast food workers tend to be among the 28 million people who are currently uninsured. Many of them are turning down Obamacare insurance – whether offered by an employer or in an exchange.

Under the new executive order, however, their employers can deposit up to $1,800 in an Excepted Benefit HRA, from which employees can purchase all types of primary care, including phone and email consultations, Uber-type house calls, the services of walk-in clinics, etc. They could also take advantage of the next option.

Free market health insurance. Historically, “short-term, limited duration” health plans have served as a bridge for people between jobs or migrating from school to work. They are not subject to Obamacare regulations and they can charge actuarially fair premiums. Although they typically last up to 12 months, the Obama administration restricted them to 3 months and outlawed renewal guarantees beyond that.

The Trump administration has now reversed those decisions, allowing short-term plans to last up to 12 months and allowing guaranteed renewals for up to three years. The ruling also allows the sale of a separate plan, called “health status insurance,” that protects people from premium increases due to a change in health condition should they want to buy short-term insurance for another 3 years.

By stringing together these two types of insurance, people will likely be able to remain insured indefinitely, with plans that look like a typical employer plan. The expected number of enrollees ranges from 1.9 million ( Medicare’s chief actuary) to 4.3 million (Urban Institute).

Yet as long as people are free to choose insurance that meets individual and family needs and as long as it is fairly priced, I think the real number will be even higher.

https://www.forbes.com/sites/johngoodman/2018/12/05/how-donald-trump-is-radically-reforming-obamacare/#4a6b0e353b2b

Altria Group (MO) to Discontinue Certain e-Vapor Products; to Take $200M Charge

Altria Group, Inc. (NYSE: MO)  announced the discontinuation of production and distribution of all MarkTen and Green Smoke e-vapor products and VERVE oral nicotine containing products. This decision is based upon the current and expected financial performance of these products, coupled with regulatory restrictions that burden Altria’s ability to quickly improve these products. The company will refocus its resources on more compelling reduced-risk tobacco product opportunities.

“We remain committed to being the leader in providing adult smokers innovative alternative products that reduce risk, including e-vapor,” said Howard Willard, Chairman and CEO, Altria Group, Inc. “We do not see a path to leadership with these particular products and believe that now is the time to refocus our resources. We recognize the impact this decision has on our employees and business partners, which we do not take lightly.”

Altria’s subsidiaries will begin working with their retailers, wholesalers, contract manufacturers and suppliers to ensure an orderly process. MarkTen cig-a-likes are currently in distribution at retail and through e-commerce. Green Smoke is primarily available on e-commerce with limited retail presence. VERVE is in limited distribution at retail and e-commerce.

Altria expects to record one-time pre-tax charges of approximately $200 million, the majority of which would be non-cash asset impairment charges, in the fourth quarter of 2018 as a result of this decision. These charges will be excluded from Altria’s adjusted results.

https://www.streetinsider.com/Corporate+News/Altria+Group+%28MO%29+to+Discontinue+Certain+e-Vapor+Products%3B+to+Take+%24200M+Charge/14901098.html