LSE claim babies born to older mothers ‘are healthier, taller AND obtain more education’


  • Women have previously been warned of delaying pregnancy 
  • But new research conducted at the London School of Economics disagrees
  • It says births postponed 10 years benefit from a decade of social changes

Children of older mothers are healthier, taller and obtain more education than children of younger mothers, according to a study.

Researchers claim health and educational opportunities steadily improve year-by-year, meaning it pays to be born later.

Most research has previously suggested that older motherhood causes a heightened probability of Down Syndrome, Alzheimer’s disease, hypertension and diabetes.

However, while not arguing against this, the latest findings by the London School of Economics and the Max Planck Institute for Demographic Research, in Germany, suggest there are also benefits.

Specifically, the fact a ten-year difference in maternal age is accompanied by a decade of changes to social and environmental conditions.

‘Those twenty years make a huge difference,’ explains author Mikko Myrskylä.

‘A child born in 1990, for example, had a much higher probability of going to a college or university than somebody born 20 years earlier.’

Scientists used data from over 1.5 million Swedish men and women born between 1960 and 1991 to examine the relationship between maternal age at the time of birth, and height, physical fitness, grades in high school, and educational attainment of the children.

Physical fitness and height are good proxies for overall health, and educational attainment is a key determinant of occupational achievement and lifetime opportunities, they said.

Most research has previously suggested that older motherhood causes a heightened probability of Down Syndrome, Alzheimer's disease, hypertension and diabetes

Most research has previously suggested that older motherhood causes a heightened probability of Down Syndrome, Alzheimer’s disease, hypertension and diabetes

They found that when mothers delayed childbearing to older ages, even as old as 40 or older, they had children who were taller, had better grades in high school, and were more likely to go to university.

 The benefits associated with being born in a later year outweigh the individual risk factors arising from being born to an older mother. We need to develop a different perspective on advanced maternal age

For example, comparing two siblings born to the same mother two decades apart, they found on average the child born when the mother was in her early 40s spends more than a year longer in the educational system.

The researchers compared siblings who share the same biological mother and father and who grew up in the same household environment.

‘By comparing siblings who grew up in the same family it was possible for us to pinpoint the importance of maternal age at the time of birth independent of the influence of other factors that might bias the results,’ said Barclay.

‘The benefits associated with being born in a later year outweigh the individual risk factors arising from being born to an older mother. We need to develop a different perspective on advanced maternal age.’

The research was published in the Population and Development Review.

Women who delay pregnancy by a decade find their children are healthier, taller and obtain more education than children of younger mothers, according to scientists

Women who delay pregnancy by a decade find their children are healthier, taller and obtain more education than children of younger mothers, according to scientists

We Could Soon Be Traveling By Hyperloop.


Elon Musk first discussed the concept of Hyperloop in 2012. Since then, he has shared detailed plans for the transportation system, which could theoretically hit a top speed of 760 mph (1,220 km/h). Two companies have plans to develop Hyperloop, and one, Hyperloop Technologies Inc., has said that there will be an operational Hyperloop somewhere in the world by 2020. The system would shoot windowless “pods” through tubes, and Musk has described it as “a cross between a Concorde, a rail gun…and an air hockey table.”

https://curiosity.com/memes/we-could-soon-be-traveling-by-hyperloop-curiosity/?_e_pi_=7%2CPAGE_ID10%2C8530788536#hyperloop-1000kmhr-ground-travel-coldfusion

 

Insurance, tax saving, expert opinion, calculators


http://economictimes.indiatimes.com/tdmcriskcalculator.cms

WADA makes meldonium U-turn, could affect Sharapova ban.


Athletes who tested positive for meldonium before March 1 could have their bans overturned less than four months before the Rio de Janeiro Olympics after WADA said it was unable to establish how quickly the drug, outlawed since Jan. 1, cleared the system.

The World Anti-Doping Agency’s notice to national anti-doping bodies is expected to have a major impact on many of the 172 athletes who have tested positive for the performance-boosting drug since January.

They include five-time Grand Slam tennis champion Maria Sharapova, who was among 40 Russian athletes to test positive for the drug after it was added to WADA’s list of banned substances in January.

Sharapova’s lawyer John Haggerty accused WADA on Wednesday of “poorly” handling the issue and said they were now “trying to make up for it”.

WADA said there was “currently a lack of clear scientific information on excretion times”.

“As a result it is difficult to know whether an athlete may have taken the substance before or after January 1, when it became illegal.

“In these circumstances, WADA considers that there may be grounds for no fault or negligence on the part of the athlete,” it said in a statement sent to anti-doping agencies and sports federations, adding that the presence of less than one microgram of meldonium in the samples was acceptable.

The anti-doping body’s notice also gave hope to athletes who have tested positive for the drug since March 1, depending on studies being carried out to determine how long it stays in the body.

Sharapova, who said she had been taking meldonium for more than a decade because of health problems, was provisionally suspended by the International Tennis Federation (ITF) in March after announcing she had failed a test at the Australian Open.

“The fact that WADA felt compelled to issue this unusual statement now is proof of how poorly they handled issues relating to meldonium in 2015,” Haggerty said in a statement.

“Given the fact that scores of athletes have tested positive for taking what previously was a legal product, it’s clear WADA did not handle this properly last year and they’re trying to make up for it now.”

Russian Tennis Federation President Shamil Tarpishchev said Sharapova’s ban could be addressed in a meeting with ITF head David Haggerty later this month.

“The situation with Sharapova could be resolved after April 21 when we meet with the head of the international federation. It is too early to talk about Sharapova competing at the Olympic Games,” Russia’s TASS news agency quoted Tarpishchev as saying.

Russian Sports Minister Vitaly Mutko welcomed WADA’s decision.

“The Russian Sports Ministry supports and welcomes the decision made by WADA because it has shown a willingness to understand the situation, rather than stick to the rulebook,” Mutko said in a statement.

“WADA has demonstrated impartiality and being objective in the fight against doping.”

Alexei Kravtsov, president of the Russian Skating Union (RSU), said that five-times world champion Pavel Kulizhnikov and 2014 Olympic short track gold medallist Semen Elistratov — both found to have taken meldonium — should be allowed to compete again after the WADA decision.

“These sportsmen should be allowed to fall under the amnesty due to the amount found in their doping tests,” Kravtsov was quoted as saying by the R-Sport news agency.

Two more Russian federations — rugby and cycling — said their athletes who had tested positive could be free to return to competition.

They include rugby player Alyona Mikhaltsova and cyclists Anastasia Chulkova and Pavel Yakushevsky who all tested positive for less than one microgram.

Meldonium, manufactured for people suffering from heart problems, can also increase blood flow and improve exercise capacity.

Giving A Voice To Rare Bleeding Disorders


Foster_Factor1

My name is Rick Kelly, and my wife, Josie, I are the proud parents of Forrest. Forrest has a rare bleeding disorder called afibrinogenemia, or Factor I deficiency. This is the story of afibrinogenemia in three anecdotes that explain what afibrinogenemia is, the current state of treatment and its outlook for the future. In sharing our family’s stories, I intend to highlight the unique challenges a tiny population with a very rare disorder experiences and outline our hopes for the future.

_______________________________________________________________

Diagnosis & Overview

In September 2013, I sat next to Josie, and our infant son, Forrest, inside a clean hospital just south of New Delhi, India. Work opportunities had taken us to India shortly after Forrest’s birth. Early on, we had a few scares with Forrest’s bleeding issues, but a lack of family history and misdiagnosis meant that we had few concerns moving to India with our precious boy.

Soon after arriving in India, Forrest – who was three months old when we moved – began developing numerous bumps and bruises across his body. We were confused and concerned as to what the problem could be, especially as neither Josie nor I knew we both carried a gene mutation that could lead to afibrinogenemia. With the encouragement of family members and friends in the medical field, we decided to seek another opinion on Forrest’s condition.

Now, sitting in the lower level of a foreign hospital almost 8,000 miles from home, we were about to hear the most dramatic news of our life.

The doctor sitting across the table cleared his throat and began, “Your son has afibrinogenemia. This is a very rare and very serious bleeding disorder that could result in major trauma or death if not treated properly.”

Josie burst into tears and I stared blankly at the doctor as he further explained the condition to us.

“Fibrinogen is also known as Factor 1. Fibrin, the protein that your son’s liver does not produce, forms the mesh across a wound that helps hold a clot in place. Fibrinogen is the last factor in the clotting cascade, and without it, the clot simply cannot form. Based on our tests, your son produces no detectable amount of fibrinogen, which means he has the most severe of cases.” Foster_Factor1

“Congenital afibrinogenemia may either occur through a gene mutation, or more likely, it is passed on to the child by both parents as it is an autosomal recessive condition. The condition affects both males and females equally, and there are fewer than 1,200 known cases in the world.”

“Look,” he continued, “I’m not going to tell you what you must do. But I can tell you that we do not have the necessary treatments for your son in India. I urge you to return home to the United States as quickly as possible.”

Within days, we were on a plane back to the US, full of questions and bursting with anxiety.

Connections and Community

Like many people managing a new challenge, we turned to the internet for support. We connected with people on Instagram and Facebook by searching #hemophilia. This group of people were our initial connection to a beautiful community of people we knew nothing about. In that community of online hemophilia, we found support and parenting tips for managing Forrest’s care. Still, we really wanted to connect with other people with Forrest’s condition.

On a cold spring morning, I laid on our couch while Forrest scooted around on a rug which sat on an extra thick carpet pad;a futile attempt to prevent bruises that come with a small child starting to explore his bodily capabilities. As many of us do or wont to do, I opened Twitter and after scanning for news, I searched for #fibrinogen. I scrolled through many posts – most of which were banal tweets from overeager AP Biology students sharing a passage from a textbook.

However, one tweet in particular caught my eye. It had been posted by someone looking for people with afibrinogenemia. I followed the account and quickly sent a message to the account owner explaining our situation. Within a few hours, we were added to an email listserv of people throughout the world that also have afibrinogenemia.

I’ve found a wonderful connection with the people on this email listserv and on a small Facebook group for people and families affected by fibrinogen problems. Like all bleeding disorders, people with fibrinogen deficiencies come from all walks of life. We’re connected to people in Japan, Switzerland, Pakistan and many more places throughout the world. Communicating with this group has been one of the personally fulfilling events of my life – not only do we receive help and advice from other people, but we’re able to make a positive contribution as well.

Throughout our communication with this group over the past two years, one thing has become certain to me – the variability of care for people with fibrinogen disorders is far too great. My son, Forrest, has a port and receives regular prophylactic infusions of fibrinogen. Others are not so fortunate. A fibrinogen concentrate has only been available for a few years in the United States, but there are many people who do not have regular access to the highest standard of medical care. My sincere hope is that the same communication channels that enabled us to connect with people suffering from the same condition will enable medical professionals to communicate fluidly enough to define standards of care for fibrinogen disorders.

Foster_Factor1Future of Treatment

By March 2015, Forrest had received a port and we (well, mostly Josie) had begun infusing him at home. Both Josie and I, along with most of our siblings, had been diagnosed with hypofibrinogenemia, which means we don’t produce normal fibrinogen amounts but we also produced some fibrinogen. By this point, we’d settled into a routine of managing Forrest’s care and had gotten involved with local and national hemophilia groups.

At HFA Symposium 2015, Josie and I attended a session on the future of hemophilia treatment hosted by a panel of esteemed medical professionals. The mood was upbeat and positive; almost universally, the doctors on the panel believed that the management of hemophilia would greatly improve over the next several years. New pharmaceutical products and potential gene therapies could mean that hemophilia would be de facto eliminated as a regular concern for most people.

I listened intently for any mention of fibrinogen conditions, knowing that the likelihood of them being discussed was unlikely. Finally, during the audience question and answer period, I raised my hand to ask a question I already knew the answer to.

“Hi, I’m Rick, and my one-year old has afibrinogenemia. Can you share your outlook for treatments for his condition? What do you think the likelihood of progress is in this area?”

I watched one of the panelists breathe deeply and then begin to speak, “Uh…that’s a good question…really, I don’t know how to say this other than the outlook for rare bleeding disorders like afibrinogenemia is about the same as it is today. Frankly, there are less than 150 known cases in the United States and I think it’s highly unlikely that most pharmaceutical companies will pursue further therapies with such a small market…I’m sorry.”

The other panelists nodded in somber agreement.

I had known the answer – that the likelihood of any progress was essentially zero – before I opened my mouth. But still, the hearing the answer caused a visceral reaction I had not expected. I felt as though I had been sucker punched.

Shortly after the panel ended, I returned to my hotel room, sat in a chair and cried for my son for a minute. He is my darling boy, and it pains me to know that treatments for his condition are unlikely to improve dramatically. But more than just Forrest alone, I feel sad for the hundreds of other people throughout the world who do not receive adequate care. There are parents like me who want not just better treatment – but any treatment – throughout the world and the United States.

Foster_Factor1

Room for Optimism

While the relatively small market size does not bode well for the pace of progress within Factor I deficiencies, there is still room for optimism. We have a burgeoning community that continues to develop online. I’m confident that increased communication between medical researchers will lead to increased standards of care that allow others to receive the same quality of care that Forrest does.

And genuinely, there are many ways in which I’m grateful for our experiences. Being so near tragedy has enabled me to be more open to life and to form deeper connections with my wife and son. When almost anything could go wrong, we find ourselves holding our son tight every night.

_________________________

Rick and his wife Josie live in California with their son Forrest.

THE TRUE DEFINITION OF SUCCESS


The True Definition of Success

 

What is the True Definition of Success? For most people, the answer to this question appears obvious.  For Most people Success is all about Fame, Wealth and Status. The reason it is their definition of success is that it is also the society’s definition of success so most people don’t even question this definition. In fact the Webster’s Dictionary goes on to define success as the attainment of Wealth, Respect or Fame

In most people’s eyes you are successful only if you have loads of cash, nice cars, a big house or multiple houses and possessions associated with a luxurious lifestyle. However, if all you follow is this definition and are willing to sacrifice everything for it, even your basic happiness, then you maybe successful at earning money but not successful at living a good life. Here are 7 key things that truly define success.

 

Making an Income You are Happy With

While only defining success though money is stupid, the fact is we all need enough money to provide a comfortable living for ourselves. Now what is defined as comfortable is totally up to you. The important thing is you should be happy with whatever you are making. Happiness is the key to success. 

When I made my movie Carve Your Destiny I interviewed some of the most famous achievers for it. Deepak Puri, the multi-millionaire chairman of Moser Baer specifically stated. “Success is to the degree you desire. Even if a man makes a limited income he is happy with and has achieved all the goals that he wants, I believe he is successful. I personally think  am not successful to this day because I still have many goals to achieve.”

A Lack of Jealousy

A lot of people say they are happy or content with whatever they have achieved in life. They say they are successful because they are happy, but the moment they see others achieving more than them, they get jealous.

It’s not that everyone needs to be at the peak of the mountain. Some have a desire to climb small mountains and others want to scale the Everest. If you are happy with it, great but if seeing a friend, an acquaintance or even an enemy achieve great heights triggers jealousy, it means you are not content, you are complacent. You are making contentment as an excuse to stay complacent and not achieve your goals.

If you are jealous of somebody else that’s the time you need to ask yourself why am I complacent and what can I do to change my situation. Then go achieve the goals you desire until a point comes that you no longer care if anyone else rises higher or not, because you know you have achieved everything you wanted in life. That’s the true definition of success.

 

Being In Charge Of Your Life

The feeling of having control over your destiny is an amazing feeling as compared to being told what to do at every point of your life.

Most people live lives where they are dictated every moment by others what to do. When you are young, you have no choice. You will be under the control of your parents and teachers. But when you are an adult you have a choice.

If you love your job and are given enough independence in it to pursue what you want happily and make a good living, there is absolutely nothing wrong with having a job, in fact this situation would be ideal for many. However, in many cases this is far from the truth.

If you are living a life where your boss screams at you everyday, deal with extreme negativity with your colleagues and break your back working hard everyday to make someone else rich are you really successful even if you make money as a result of your miserable life? I think not. Think about starting a business or doing something on your own.

Overcoming Challenges

If you were born in a family where your daddy had a net worth of $950 million, I wouldn’t call you a success just because you ended up having a net worth of $1 billion.

On the other hand if you were born in an extremely poor family, had to endure abuse, did not get proper education, faced numerous personal tragedies, faced rejection at every stage and yet you overcome all those immense challenges to now reaching a position where you are employed in a respectable job or running a successful small business, in reality you are much much much more successful than the guy who inherited a billion dollars. This is the true definition of success.

Success is not about what is handed down to you on a platter, it is about what you are able to create out of almost nothing despite facing pain, hardship, rejection and despair at every corner. It is not defined by what you achieve in life, but the obstacles you overcame to achieve what you finally did.

 

Having a Great Family and good health

If you don’t have support from your family or if things are always combative, you can have a big house, a big car and a big bank balance and you will still be miserable. In fact this is indeed the case in many families that are actually extremely well off financially.

People are after the money but ignore the relationships. As a consequence they suffer. They don’t spend time with their parents, their spouses hate them and their children could care less. The divorce rates are going up  especially in high income groups and relationships between children and their parents are getting worse. What’s the point of this kind of success?

Invest your time in relationships if you want to have a truly successful life. You cannot change a person completely but often times the way they behave with you is a reflection of how you behave with them

Doing What Matters To You The Most

Each one of us has something that we truly love doing or are extremely passionate about. Even if you have not discovered it yet, chances are there is something or the other that you are so tremendously good at and would enjoy doing that so much that it could become the mission of your life. Chances are there is something that once discovered and pursued would give you tremendous happiness and fulfillment in life. Working on it would be so effortless that it almost not seem like work. And if you can figure out how to make money while doing it, well that is the true definition of success.

However, most people are not doing what matters to them the most or pursuing their passion. For some reason, it is believed that most people have no idea what they are passionate about or what matters to them. Actually, this is far from the truth. Most people have at least SOME idea about what they are passionate about and what really matters to them.  The problem is that they lack the courage to pursue it or give up too soon. When you do what truly matters to you, the journey won’t be easy, but it will be worth it.

However, there is a strategy to following your passion smartly. Jumping in emotionally won’t cut it. Read about how to follow your passion the smart way.

 

Building a Legacy You are Proud Of

Everybody wants to be remembered in some way or the other. Most people want to be remembered for good things. This is what separates us from animals who don’t even think of the future or couldn’t care less.  People on the other hand care about the world thinks of them, and if taken in a positive way, this would motivate you to build a legacy you are proud of.

Now a legacy does not mean having monuments built in your name. That’s for the world to decide not you.  Honestly you shouldn’t even care. You should focus on doing the things that matter to you and help make the world around a better place. It does not have to be on a mass scale, it can be in your own little way. But truly what defines success is when you make the world a better place so that when you go, people say “he was a good man who had an unbelievably positive impact on my life.”

Being a person who only cared about wealth and status and ran after money without genuinely impacting people’s lives is will leave behind a worthless legacy. If you run after materialistic success, you die when you die. But when you focus on helping the world, you continue to live on in the minds and the hearts of people you impacted. Now that is the true definition of success.

 

 

 

Where to Turn for Second-Line Cytoreduction After Hydroxyurea in Polycythemia Vera?


 The goals of therapy in patients with polycythemia vera (PV) are to improve disease-related symptoms, prevent the incidence or recurrence of thrombosis, and possibly delay or prevent the transformation into myelofibrosis or acute myeloid leukemia (AML). Cytoreductive therapies have been used in older patients and those with a history of thrombosis to achieve these goals. Hydroxyurea (HU) remains the first-line cytoreductive choice; however, up to one in four patients treated with HU over time will develop resistance or intolerance to HU. More importantly, patients who fail HU have a 5.6-fold increase in mortality and a 6.8-fold increase risk of transformation to myelofibrosis or AML; therefore, alternative therapies are needed for these patients. Interferon-α has been used in PV and has shown significant activity in achieving hematologic responses and decreasing JAK2 V617F mutation allele burden. JAK inhibition has also been investigated and recently garnered regulatory approval for this indication. In this review, we will discuss the current treatment options that are available for patients after HU and the novel therapies that are currently under investigation.

Implications for Practice:

The outcomes of PV patients who fail or who are intolerant of hydroxyurea are poor. Although pegylated interferon can be considered in younger patients, currently, ruxolitinib is the only U.S. Food and Drug Administration-approved agent in this setting, representing a viable option, leading to hematocrit control and a reduction in spleen size and constitutional symptoms. Although a small number of patients will achieve a molecular response with continuous treatment, the implications of such response on the clinical outcomes are still unknown. Patients whose disease is not adequately controlled with ruxolitinib, or who lose their response, can be treated with low-dose busulfan or pipobroman; however, they should be encouraged to participate in trials with novel therapies.

Sentinel Lymph Node Mapping in Endometrial Cancer: An Update


 Lymph node removal for staging, as part of the initial surgical management of patients with endometrial carcinoma, remains a controversial topic in gynecologic oncology. There is currently wide variability among clinical practices, with surgical approaches ranging from no nodal evaluation to comprehensive pelvic and aortic lymphadenectomy. Lymphatic mapping has emerged as an increasingly popular option over the past few years, with several attractive features in its concept, innovative surgical approach, and encouraging preliminary results. At this time, however, several different techniques have been described and used for lymphatic mapping in endometrial cancer, incorporating a variety of mapping agents and injection sites. Although recently published results are encouraging, they are limited to single-institution series or multi-institutional collaborations undertaken without the aegis of a prospective randomized controlled trial. However, the surgical staging of endometrial cancer with lymphadenectomy was historically established based not on randomized trial data but on prospective clinicopathologic studies. Another evolving field in endometrial cancer staging is the interpretation of pathologic ultrastaging of sentinel lymph nodes (SLNs), which can identify low-volume metastases for which the clinical significance and the ideal management remain uncertain. This is particularly an issue with extremely low-volume nodal metastasis and isolated tumor cells. Furthermore, it has become apparent that applying a predefined SLN algorithm can decrease false-negative rates. The Memorial Sloan Kettering Cancer Center SLN algorithm can be used as a checklist to ensure standardization of care and to reduce the chance of missing nodal disease. Prospective trials are under way at many institutions to help establish the definitive role of SLN mapping for staging of endometrial cancer. The objective of this study was to provide an update on the latest clinical data related to lymphatic mapping for the staging and management of endometrial cancer and its role in clinical practice.

Implications for Practice:

Lymphatic mapping is an increasingly popular option in the surgical treatment of endometrial cancer. The aim of using this tool is to target the lymph nodes that are the most likely to be involved with metastatic cancer cells (sentinel lymph nodes) and thereby limit the extent of surgery needed and decrease surgical complications and long-term side effects associated with extensive lymph node removal. By examining a limited number of sentinel lymph nodes, a more detailed examination of the node can be done (ultrastaging). This allows for the detection of a small number of cancer cells (low-volume metastasis) that can be missed with standard techniques.

The Human Papillomavirus Vaccine: Current Perspective and Future Role in Prevention and Treatment of Anal Intraepithelial Neoplasia and Anal Cancer


 The incidences of human papillomavirus (HPV)-related anal cancer and its precursor lesion, anal intraepithelial neoplasia, are rising in the U.S. and globally. Five-year survival rates with current modalities of treatment for anal cancer are generally favorable for localized and regional disease. For metastatic disease, the relative survival rate is poor. Major contributing factors for the increase in anal cancer incidence include increasing receptive anal intercourse (hetero- and homosexual), increasing HPV infections, and longer life expectancy of treated people who are seropositive for human immunodeficiency virus. Because treatment outcomes with systemic therapy in patients with advanced disease are so poor, prevention may be the best approach for reducing disease burden. The association of a major causative agent with anal cancer provides an excellent opportunity for prevention and treatment. The advent of the HPV vaccine for anal cancer prevention and treatment is a significant milestone and has the potential to greatly impact these cancers. The data regarding potential use of the HPV vaccine in anal cancer prevention and treatment are reviewed.

Implications for Practice:

The incidences of human papillomavirus (HPV)-related anal cancer and its precursor lesion, anal intraepithelial neoplasia, are on the rise in the U.S. and globally. Based on recent studies, the HPV vaccine is approved for prevention of the infection and development of HPV-related anal cancer. In addition, several small studies have shown that the vaccine may be useful as adjuvant therapy for anal cancer. There is a need for public health strategies aimed at education of both patients and practitioners to improve the use of the vaccine for prevention of HPV-related anal cancer. The development of a therapeutic vaccine is a work in progress.

Cardiac Safety of Paclitaxel Plus Trastuzumab and Pertuzumab in Patients With HER2-Positive Metastatic Breast Cancer


Abstract

Introduction.

Myocardial strain imaging and blood biomarkers have been proposed as adjuncts to left ventricular ejection fraction (LVEF) monitoring for the early detection of cardiotoxicity during cancer therapy. We report the results of a preplanned cardiac safety analysis of global longitudinal strain (GLS), and troponin-I (TnI) and brain natriuretic peptide (BNP) levels in the phase II study of paclitaxel, trastuzumab, and pertuzumab (THP) for metastatic HER2-positive breast cancer.

Patients and Methods.

Patients with 0–1 lines of prior therapy were treated with weekly paclitaxel (80 mg/m2) plus trastuzumab (8 mg/kg loading dose followed by 6 mg/kg) and pertuzumab (840 mg loading dose followed by 420 mg) every 3 weeks. Exploratory endpoints were GLS measured with speckle-tracking echocardiography every 3 months and TnI and BNP levels measured every 6 weeks (immediately pre- and postchemotherapy infusion) at 6 time points.

Results.

Sixty-seven of 69 enrolled patients were treated with THP: 19 (28%) had hypertension, 8 (12%) had diabetes, 11 (16%) had hyperlipidemia, and 26 (38%) had smoking history. After a median follow-up of 21 months (range: 3–38 months), no patients developed symptomatic heart failure. Two patients (3.0%) experienced asymptomatic LVEF decline (grade 2). The mean GLS (±SD) was 19% ± 2% (baseline), 19% ± 2% (month 6), and 19% ± 3% (month 12). Detectable TnI (>0.06 ng/mL) and elevated BNP (>100 pg/mL) levels were observed in 3 (4.3%) and 2 (3.0%) patients, respectively, but were not associated with LVEF decline.

Conclusion.

The absence of any significant changes in GLS and cardiac biomarkers (TnI and BNP) further support the cardiac safety of THP in patients with metastatic HER2-positive breast cancer.

Implications for Practice:

Dual anti-HER2 therapy with trastuzumab and pertuzumab in combination with taxane-based chemotherapy improves overall survival in patients with metastatic HER2-positive breast cancer. There is a critical need to investigate the potential cardiotoxicity of dual anti-HER2 blockade, given the importance of HER2 signaling in cardiac homeostasis and stress response. Global longitudinal strain and cardiac biomarkers have been proposed as adjuncts to left ventricular ejection fraction for the early detection of cardiotoxicity. In this phase II study of combination trastuzumab and pertuzumab with paclitaxel, no clinically significant change was observed in global longitudinal strain or cardiac biomarkers. These results further support the cardiac safety of dual anti-HER2 blockade previously reported in the CLEOPATRA study. The findings in the current study also call into question the role of intensive cardiac monitoring among patients treated with anti-HER2 therapy in the absence of anthracyclines. Less frequent cardiac assessments could lead to a reduction in unnecessary treatment interruption and is an important consideration given the rise in medical expenditures, but this requires further investigation.