Less Chemo for Breast Cancer?

Less Chemo for Breast Cancer?

Nobody likes chemotherapy: not patients, and not oncologists.

We’d all rather avoid it if we can – and now we’ve identified another group of women who can safely do without it.  

Some early-stage breast cancers can spread throughout the body before the tumor is removed surgically– even before the cancer is diagnosed. Those small, spreading cells (called micrometastases) aren’t detectable by current technology. But micrometastases can seed tumors that show up a few years later in the bones, liver, or brain – and ultimately cause death.  

If we give chemotherapy to patients who have micrometastases, we can kill off those little seeds before they take root and improve the chances of cure. But it’s only worth it if the risk of having micrometastases in the first place is sufficiently high – usually around 18% or more. That’s why accurately predicting risk is so critical in treating early stage breast cancer. 

So for people at high risk of having micrometastases (e.g. those with lymph node involvement, or high-risk mutations on the Oncotype test), we recommend chemotherapy.  

For people at low risk of micrometastasis, we don’t. 

So what’s the news flash?  

The Oncotype test reports a patient’s risk of micrometastasis as low, intermediate, or high. We’ve always known what to do with the low and high risk patients, but we’ve been less certain about the intermediate risk group.  

But the largest trial of its kind was just reported in the New England Journal of Medicine, and it looks like we can safely skip chemotherapy in Oncotype-intermediate patients. 

Bottom line: 

  • Women with early-stage breast cancer only seem to benefit from chemotherapy if they have lymph node involvement, or if the Oncotype test indicates they’re at high risk for micrometastases. 

How do checkpoint inhibitors work, anyway?

How do checkpoint inhibitors work, anyway?

Picture a common movie scenario: the police have the bad guys surrounded, locked down inside a building – but there are hostages in there too, and if the cops go in shooting they won’t be able to tell the victims from the villains.

“Die Hard”, “Inside Man”, and “The Dark Knight Rises” have all done variations on this idea. I bet you can even think of a few more. 

But this familiar movie scenario can help us better understand the difficulty the immune system has trying to fight cancer, and how the new class of cancer drugs called checkpoint inhibitors can overcome it.  

So, let’s apply our “bad-guys-with-hostages standoff” analogy to an immune system trying to eradicate cancer, and see what we can learn:  

  1. Your immune system, like a good police officer, must sometimes restrain itself. A SWAT team storming in at every opportunity can cause terrible collateral damage, just as an unrestrained immune system can cause terrible diseases like rheumatoid arthritis and lupus. That’s why your immune system’s T-cells have special receivers sticking out of them like antennae dishes, listening for the signal to “stop” – and when the T-cell gets that signal, it backs off. We call these “stop signal” receivers checkpoint inhibitors – one of which is PD1. 
  2. Some cancer cells fool the immune system the same way the villain fooled Bruce Willis in “Die Hard”. When Bruce Willis’ character got the drop on the main villain Hans Gruber (who he’d spoken to but never seen), Hans faked an American accent and passed as a hostage (“Oh no please don’t shoot, you’re one of them aren’t you…”). In a similar way, some cancer cells have learned how transmit the “stop” signal by making a special molecule that sticks from its surface and binds to PD1 on attacking T-cells – which turns them off. We call this “stop signal” molecule PDL1. 
  3. Preventing the PDL1 “STOP” signal from reaching T-cells invigorates the immune system enough to attack some cancers Drugs like nivolumab and pembrolizumab (which interrupt the PD1/PDL1 interaction) put the fight back into the T-cells, allowing them to attack the cancer – but with much less of the “collateral damage” that we’ve seen in other types of immune enhancers.  

Here’s a video that explains the process visually. 

We should celebrate the success of these drugs, but have to remember that no cancer drug in history has ever been a “cure-all”. We have to remember that there a great many more checkpoint inhibitors than PD1, so there’s many other ways for cancer cells to escape the immune system.  

We have to remember we still need good clinical trials, and patients willing to participate in them.

(Up Next: Pembrolizumab approved for a slew of cancers all at once)

Cancer Pain

Cancer Pain

Whenever I meet a new cancer patient, especially one with incurable cancer, pain always comes up in the conversation – whether they have it or not.

It’s the most commonly reported symptom of cancer, and it’s also one of the most widely feared.  

Most patients with advanced stage cancer do, in fact, experience pain; 75-90% according to a 2007 cohort study conducted in the Netherlands and published in the Journal of Pain and Symptom ManagementAnd for much of the history of cancer medicine, most of these patients suffered terribly during their illness – and many died in agony – before the importance of relieving terminal cancer pain was widely accepted. It’s little wonder that the hospice movement began first among cancer caregivers who’d borne witness to one painful death too many and rose en masse to say “enough, no more.” 

Despite the strides made in the last half-century, there’s still a lingering belief out there that having cancer means unrelenting pain– but I’m happy to tell you that hasn’t been true for a long time. 

In honor of Cancer Pain Awareness Month, here are a few important facts about cancer pain (some of which might surprise you): 

  • Cancer pain can almost always be controlled. Data from the World Health Organization shows that following simple treatment guidelines and using widely-available medications controls cancer pain over 90% of the time. 
  • Though narcotics are usually required to control cancer pain, addiction rates are extremely low in cancer patients – probably no higher than 4% according to several studies. That’s 5-10 times lower than the addiction rates among patients with other types of chronic pain. 
  • Pain relief doesn’t require that patients be “drugged out”.  Pain medications can certainly cause sleepiness, for the majority of patients this is short-lived and can be counteracted by dose adjustment. 
  • Dying in pain is a thing of the past. With good hospice care, no one need suffer when dying. 
  • Using narcotics DON’T hasten death. The best evidence indicates that dying patients – even comatose ones – live longer when given narcotics to control pain.

Cancer: Written in the Stars?

Cancer: Written in the Stars?

Among other things the summer equinox means

(besides the sunlight fracturing my sleep at 5:30 in the freaking morning), star-gazers know that the sun’s most northerly position on the day of the equinox is in Taurus – though it wasn’t always so. In ancient Greece, the sun would’ve ridden to its equinox peak in a different constellation: specifically, Cancer. When I stumbled on that tidbit in the paper yesterday, I was reminded how long that name’s been with us.

Cancer’s new prominence in the modern age – in incidence, and in awareness – often fools us into thinking it’s a new illness; but in fact, the disease is as old as our species. It was first named in the fifth century B.C.E. by Greek physicians in the Hippocratic tradition who, frustrated in their attempts to pry tumors free of their patients, called them karkinos (“the crab”) because of the tumors’ claw-like grip.

Greek knowledge formed the basis of much of Roman learning. As Hellenic power waned and Roman influence dominated the world, the Greek word for the disease was eventually replaced by the Latin synonym for crab: cancer.

There may even be another reason these tumors reminded Greek physicians of a crab, though I’ve no proof of this. In mythology, the goddess Hera tried to foil Hercules at every turn – and during his battle with the Hydra (when he needed all his wits and strength) she sent a large crab to bite at his feet during the battle, hoping it would affect his footing enough to cause his defeat. When Hercules instead crushed the crab, myth says Hera memorialized it in the heavens as one of the signs of the Zodiac.

In Hippocrates’ time lifespans were much shorter so cancer would’ve been rare, and would’ve affected the young and otherwise healthy. It would’ve seemed a random calamity of cosmically cruel proportions, biting at the heels of otherwise vibrant youth – like the one Hera sent to torment Hercules – and just like pediatric cancer still seems to us today.

FLT3 mutations in AML: From Trivia to Triumph

FLT3 mutations in AML: From Trivia to Triumph

Here’s an aggravating fact about medical education – a large chunk of what’s taught in medical school is useless trivia:

  • The muscle that elevates your palate is called the tensor veli palatini…
  • Here’s the best way to treat leprosy…
  • Adults whose acute leukemia cells carry an internal tandem mutation of the FLT3 surface tyrosine kinase have a worse prognosis…

I and other cancer specialists have known that last little nugget for about ten years, but haven’t been able to do squat with it:

“So should I use a different induction chemotherapy for FLT3-mutants?” (No)

“Should all FLT3 mutants get a stem cell transplant?” (Not necessarily)

“Is there anything I can do differently for these patients?” (Silence)

Thanks. Thanks a fricken’ lot.

It’s a little unfair to rant, I know. There’s a long lag time between discovery and new treatments for cancer -but the wait is hard, especially with new leukemia patients coming in the door every month.

But last week finally – finally – a drug targeting this specific molecular defect was approved by the FDA.

See, FLT3 is like an “on” switch for cell division. It’s supposed to only be on when it gets a particular environmental signal, and not every cell even carries the switch. But about 35% of acute myeloid leukemia patients have FLT3 abnormally expressed in their cancers – and the switch is stuck in the “on” position, driving cancer cell growth.

Happily, the new FLT3-inhibiting drug midostaurin (given as a twice-daily pill) markedly improved response and survival rates in AML when added to the standard chemotherapy cocktail. The benefits seemed most pronounced among people who ultimately went on to receive a stem cell transplant – but a higher percentage of patients were able to achieve the remission usually required as a first step before transplant.

So now I can re-categorize the FLT3 information from “trivia” to “critical information” in my brain, as I impatiently wait for more breakthroughs.

FDA Press Release 4/28/17: click here

Henrietta’s Still With Us

Henrietta’s Still With Us

HBO’s newest movie “The Immortal Life of Henrietta Lacks” (seen here)  tells how one woman’s death from cervical cancer in the segregated South of 1951 helped fuel generations of scientific discovery – though she never gave permission for her specimens to be used in this way.

 Here’re a few things to know:

  • Most cancer cells can’t survive outside the human body. Cancer cells are more fragile than most people realize, and can’t survive the harsh conditions in the test tube for very long. The vast majority of cancer cells harvested from patients die after only a few hours, but Lack’s cells (dubbed HeLa cells) survived indefinitely. This allowed researchers to observe multiple generations of cell division, and begin to understand that cancers evolve over time similar to the way species do. That’s what made the HeLa cells so unusually valuable.
  • In 1951, researchers didn’t need permission to obtain tissue specimens for research. When Dr. George Gey, a researcher at Johns’ Hopkins, realized the potential of Lacks’ uniquely aggressive cancer, he sent his lab technician down to the morgue to retrieve more specimens. It never occurred to either of them to ask for her family’s permission – and as distasteful as that seems to us today, informed consent wasn’t required for medical research until the the National Research Act passed in 1974.
  • Henrietta Lacks’ story wasn’t known outside of scientific circles until 2000. The story gained general notoriety with the publication of Rebecca Skloot’s book The Immortal Life of Henrietta Lacks (available here: https://www.amazon.com/Immortal-Life-Henrietta-Lacks/dp/1400052181/ref=sr_1_1?ie=UTF8&qid=1493146609&sr=8-1&keywords=the+immortal+life+of+henrietta+lacks).
  • The scientific community failed to protect the Lacks family’s privacy. Science can work very efficiently when information is openly shared. But since the genetic information about an individual or family can potentially lead to insurance discrimination, such data must be treated carefully. Unfortunately, details of Henrietta Lacks’ genetic information were widely circulated  on the internet before the need for this kind of discretion was generally appreciated – and it wasn’t secured until 2013.

Henrietta Lacks’ story holds special interest to me for a couple of reasons: first, I worked with the HeLa cell lines (among others) while a postdoctoral fellow at the Mayo Clinic; and second, a college friend of mine served as Johns Hopkins Medical Center’s official liaison to the Lacks family, and wrote a book about their reminiscences of Henrietta (which you can get here: purchase book).

I hope that Henrietta Lacks is somewhere, somehow aware of her rich scientific legacy – that her tragic and premature death from cancer has taught us how to save others – and that she’s managed to forgive science for its sins against her.

 

What More Can I Do? World Cancer Day 2017

What More Can I Do? World Cancer Day 2017

After a certain point awareness just wears us down.

Like comedian Doug Stanhope, when I see the ribbons and vigils and observances I sometimes think “could we be doing anything with less impact?”

In the last ten years I haven’t met anyone over the age of five who isn’t aware of cancer, so – check – mission accomplished.

But World Cancer Day asks for more than just awareness. It asks us to take actual steps to reduce the impact of cancer for ourselves, our communities – hell, our whole species. So as a part-time cancer caregiver (and a full-time mortal with a high probability of being an eventual cancer patient) I’ve come up with three areas to focus on:

Don’t tempt the gods 

We can’t be rid of cancer entirely, since it’s one of the ways our body naturally unravels, but too many of us are dying too young because of avoidable risks.

  • Obesity: we’re only beginning to understand how this works, but the link is beyond all doubt – and that’s bad news since obesity’s now a worldwide epidemic. The good news is this one’s still firmly in our control, if we can muster the will and discipline.
  • Alcohol: like many fellow cheeseheads, I sometimes overdo it. It’s not as much fun as it used to be, and it increases my risk of throat, liver, esophagus, and colon cancer 2-3 fold. Is it really worth all that?
  • Tobacco: I’m an ex-smoker who still misses it, so I get it, I really do. But there’s just no safe level of tobacco use. We can and should retain the right to make our own choices – but quitting is among those choices, and newer therapies make quitting more achievable than ever.

Stop pretending resources are unlimited 

Conservative estimates predict that by 2020 we’ll spend 39% more on cancer care in the United States than we did in 2010, to the tune of $173 billion dollars. (full article: click here) And though I’m no economist, I get the distinct impression that we just don’t have that kind of money to throw around anymore.

Yet every day I see unnecessary waste: labs drawn daily on hospital patients out of habit, PET and CT scans ordered when there’s no probability they’ll change our understanding, and expensive tumor genetics testing ordered when it can have little impact on choosing proper treatment.

So from now on I’m going to start each day by remembering what one of my medical school mentors used to say: “if you can’t explain in one sentence how a particular test could change your decision, you don’t need it.”

Earn back medicine’s credibility 

Medical professionals do not and have never deserved reverence or obedience.

In the Hippocratic tradition physicians were humble servants. But somewhere down the years we got a little too enamored of our growing knowledge, a little too excited by new tools and techniques, and a little too stuck on the idea of being saviors. Today, patients rightly fault us for communicating poorly, keeping them uninformed, and ignoring their priorities. Is it any wonder that most cancer patients use some form of (largely untested and unproven) complementary treatment?  Or that clinical trials participation is at an all-time low? Or that long-proven measures like vaccination are increasingly abandoned?

I need – we all need – to remember our place as physicians. We’re supposed to serve patients’ goals and priorities, not our own. We’re supposed to give ear to patient’s stories of their illnesses, and the meaning they make of them.

Though science does indeed have a powerful story to tell about cancer, physicians must earn back the right to tell it by relearning how to listen.

Dear Cancer Patient – Finishing Up

Dear Cancer Patient – Finishing Up

Dear Cancer Patient,

You probably thought this day would never come, but you’re finally finishing treatment. Well done!

You probably expected to feel only relief, but don’t be surprised if it’s mixed with a little anxiety. Treatment can become a kind of security blanket, a trusted shield against the cancer – and now it’s going away. Being on treatment made you feel safe, and now you feel unsafe.

But your treatment was meant to mop up the last traces of the cancer – nothing more, nothing less. You’re not really losing ongoing protection, you’re just losing the illusion of protection, just as you’ve been stripped of many illusions by this experience.

You’ll also probably want to ask me if it’s all really gone forever, if you’re “cancer free”, and what tests we’re going to do to find out. And I must tell you there is no possible way for us to know right now if you’re cured, or if you’re not. I wish there were. We can only know that we’ve done everything possible to cure you, and to secure your future cancer-free state. But we can’t know that future until it arrives. We’ll find out what that future is together, over time.

Can you still remember when you believed that cancer could never happen to you? It never entered your thoughts that those normal aches, pains, or energy lulls could be cancer – and of course they weren’t. But now, when those aches and pains come, cancer will cross your mind. Because you know now that such things are possible. You’ve lost the sense of safety you had before the cancer came, but that’s only because the idea of safety itself is an illusion – and it’s only the illusion that you’ve lost.

This is nothing to grieve, but it does take some getting used to. Living without illusions takes courage. Living without illusions is also known as wisdom, or so I’m told. I don’t know personally, because I’ve not had your experience yet. The only things I know about wisdom I’ve learned from you, and those who came before you.

It’s almost time for you to go, and I’d like to send you off with some impossible advice: take this experience and make it part of your identity, let it be written into your lines and verses; and also try to forget about it as soon as possible – it looms too large in your mind right now, and after all it’s only a few verses in a very long song.

I’ll be here if ever and whenever you need me. But right now I’m going to walk you to the door because it’s time.

Go now, and live.

Affectionately,

Your Devoted Oncologist

 

Dear Cancer Patient – Mid-Treatment

Dear Cancer Patient – Mid-Treatment

Dear Cancer Patient,

Treatment’s been underway for a while now. As things have gotten a little more routine, you might have noticed your worries have shifted.

See at first, most people are scared of the treatment itself, worrying about nausea and infection and every possible side effect under the sun. But when those things don’t materialize, the idea of reducing or skipping a dose becomes the scarier prospect.

“But I’m feeling fine,” I’ll hear people say when I tell them their white blood cell count is a hair too low for treatment today. “I don’t feel sick, and I want to keep fighting my cancer. Wouldn’t it be better if we just went ahead? I don’t want to give up.”

The reversal is interesting, isn’t it? And it’s perfectly understandable; humans adapt amazingly well to their circumstances – any circumstances. So fear comes from behind us and in front of us, not from the place we’re at.

This is when you must remember that chemotherapy is delicate, and needs tailoring to you individually – a nip here, a tuck there – so that you can stay safely on track. If we press on when your bone marrow or weight or some other indicator are flashing warnings, it’s more likely you’ll get an infection, or wind up in the hospital, or get so worn down that you won’t be able to complete treatment at all.

Practically speaking, all cancer treatments must first and foremost be tolerable. An d a great deal of that tolerability comes from the nuances of how it’s given, and modified according to side effects. Years of experience have taught your doctor and your team when to push, and when to take a breather.

Our goals haven’t changed. We’re still after the same thing we were at the beginning.

Every boxer knows when to jab, when to lunge – and when to take a step back. You’re team isn’t giving up on you. More than likely, they’re setting up a counter-punch.

That’s not giving up.

It’s fighting smart.

 

Sincerely,

Your devoted oncologist

Dear Cancer Patient – Starting Chemotherapy

Dear Cancer Patient – Starting Chemotherapy

Dear Cancer Patient,

You’ll be starting chemotherapy soon, and you’re nervous – and after everything you’ve been hearing about it that’s understandable.

I’m not going to tell you that we don’t need to be careful with these drugs, or that there are no side effects, because that’d be a lie. But I’d like to wind back some of the overblown scary things you’ve been hearing:

First, just because you’re getting treated for cancer doesn’t mean you’re made of glass. For the most part, you can live life just as you did before. If there’s something specific you need to change, I or someone on my team will tell you.

Second, there isn’t now (and never was) a need to be a germaphobe. Wash your hands when and how you’ve already been taught, kiss the people you usually kiss, and go the places you usually go. It’s simply untrue that you should avoid crowds, or stop going to church, school or the movies. I’ve sometimes overheard well-meaning medical people tell patients that – while they talked in the middle of a crowded medical office. I wish they’d stop saying stuff like that.

Third, you probably don’t need to dramatically change your diet, assuming it was reasonably healthy to begin with (if not, take it easier on the greasy stuff for a while). But know that your taste buds and gut are going to be unpredictable for a while. Things might not taste the same, and some former favorites might send you dashing for the loo after a few hours – something those of us fond of raw seafood and volcanically-hot Thai are familiar with. For most people, it’s mildly inconvenient, but doesn’t cause lasting harm. Just pay attention to what triggers those episodes, and adapt. You’ll be fine.

There are two main reasons why chemotherapy gets a bad rap. The first is because it isn’t always clear to observers whether it’s being used to cure cancer, or delay the progression of incurable cancer. In the latter setting, people still decline gradually and ultimately die, it’s just a more gradual decline with the treatment in most cases.

The second reason is an ugly truth about cancer medicine’s past. Sometimes, oncologists got so carried away with trying to shrink tumors that they failed to pay attention to how it was affecting the individual patient. Sometimes, they’d keep treating even when patients were getting worse – because the tumor was shrinking.

Oncologists have been guilty of sometimes making the treatment worse than the disease – but times have changed. I promise you I’ll never do that, not here, not today, not EVER.

If treatment ever makes things worse instead of better, I’ll change your treatment.

 

Sincerely,                                                                                                                                                                           Your Devoted Oncologist