Male Breast Cancer

Male Breast Cancer

Men absolutely get breast cancer. It happens here in Green Bay.

I’ve treated it. So it’s absolutely a thing.

But men get breast cancer about 100 times LESS often than women do, for a very simple reason:

Most breast cancers develop from abnormal cells in the ductwork of the breast. But men have less breast ductwork to begin with – so they get breast cancer less often. It’s kinda the same reason you see fewer cheesehead hats in Florida…there are fewer Packer fans in Florida to wear them.

Since cancer screening only works in a high-risk population, and the risk for breast cancer in most men is so low–screening for breast cancer with breast exams and mammograms and such isn’t usually recommended (or even a good idea) for most men.

The exception is men who carry mutations that increase the risk of cancer, such as the BRCA mutation (specifically, the BRCA2 mutation). There are other mutations that also increase breast cancer risk, but that’s the most relevant one for men. The association between BRCA mutations and male breast cancer is so strong that having a male relative with breast cancer is usually a good enough reason to consider getting tested for the mutation.

Having said all that, once a man gets breast cancer–the treatment for it is remarkably similar to the treatment for women. This is because these cancers, whether they appear in a man or a woman, are driven by similar biological mechanisms, tend to spread in similar ways, and tend to respond to the same kinds of drugs.

One caveat to that general rule of treatments being more alike than different for men and women is that most men need mastectomy (removal of the whole breast) rather than lumpectomy (removing only the affected part of the breast) – but this is simply due to the fact that men generally have less breast tissue to work with than women do.

Estrogen blockers (like tamoxifen and aromatase inhibitors like arimidex and letrozole) work in most male breast cancers as well as they do for most female breast cancers. That surprises people because we tend to think of estrogen as the female hormone and testosterone as the male hormone, and tend to forget that both men and women have lots of both. It’s just the relative mix of the two hormones that’s different between the sexes–and that mix changes as we age.

Has COVID-19 lost us the war on cancer?

Has COVID-19 lost us the war on cancer?

For several months in the spring of 2020, clinics and hospitals across the United States temporarily suspended routine cancer screening during the early phase of the COVID outbreak. Patients we’d reminded by mail and phone not to forget their mammograms or colonoscopies or PAP smears were suddenly told to cancel them and sit tight.

Most places have now resumed routine cancer screening, but the pause understandably raised lots of questions:

  • “Did the delay put me in danger?”
  • “Will there be a spike in advanced cancer cases now?”
  • “If this was so important, why was it delayed in the first place?”

A recent article in the Milwaukee Journal Sentinel suggested the delay might have cost us the chance to cure people. But there’s reason to doubt this.

Cancer screening depends on—and only works for—cancers that grow and spread slowly in the early stages. The most common types of breast, colon, lung, and cervical cancer take a few years to become dangerous. This long lead time is the very reason screening is possible. It’s also why it’s hard to see how a 3-6 month screening delay could be enough to allow a significant number of early-stage cancers to become incurable.

Right now you’re probably asking, “don’t some cancers appear more quickly and spread more aggressively than the usual type?”

Yes, there’s an exceptional minority of cancers that can appear and spread rapidly, sometimes within a few months. But screening doesn’t work for these aggressive cancer sub-types, and it never has. Cancer screening was never designed with this tragic minority in mind, since we have so little power to alter their clinical course.

I’m not worried about the brief interruptions in cancer screening we experienced earlier this year, since services have mostly resumed and we’re able to get back on track. I’m more worried that many of us will conclude cancer screening couldn’t have been important in the first place, if we can safely pause it—and that patients won’t reschedule. I fear that public skepticism and reactive rhetoric might interfere with cancer screening long enough to matter.

If we lose the war on cancer over this, it’ll be because we surrendered what cancer screening had already won for us.

No Illusions

No Illusions

Though I’m an oncologist and not an infectious disease expert I’m getting bombarded with questions about the pandemic. Patients and staff are asking me and every one of my partners similar things, over and over:

How long until things go back to normal?

How much danger am I in?

Is it all going to be ok?

Though I’m supposed to have all the answers, I haven’t felt too sure of anything lately. It must show on my face, because recently one of my patients (a young woman living with incurable breast cancer) asked “how you doing there, doc?”

“Honestly, I’m not sure,” I said. “My regular routine is wrecked, I don’t feel as safe as I used to, and I don’t know what’s coming.”

“Welcome to my world,” she said, with a wry smile.

I suppose like everyone else in my privileged corner of the planet, where war is remote and epidemics are rare, I’ve been fooled into believing that the world is a safe place, that nature wants the best for us, and that we have control.

Somehow I’ve mistaken privilege for entitlement.

But the pandemic has stripped those illusions from me, just as cancer stripped them from my patient long ago. I’ve had to accept that there’s no such thing as safe – only safer. I’ve had to admit that I don’t have as much control as I’d like. And I’ve had to consider the very real possibility that I or someone I love might not survive.

And even if we and all our loved ones come through safely, somehow I doubt we can ever go back to the sleepy (and false) security of before. We may well divide our lives into distinct sections: “Before COVID” and “After COVID”, just as many patients have distinct lives before and after cancer.

And maybe we’re better off living without illusions of safety.

If life becomes more precarious, maybe it’ll also be more precious. Maybe in facing the truth of our mortality we’ll learn a deeper compassion for all survivors, everywhere – since every human breathing is a survivor of something. And if I’m spared, perhaps the me that comes after will have learned to live with more dignity and courage.

Maybe my patient will teach me.

Paddleton: Being There is Everything

Paddleton: Being There is Everything

“I’M the dying guy!” Mark Duplass’ character screams at his best friend, played by Ray Romano.

“I’m the OTHER guy!” Romano’s character screams back.

Paddleton, a low-budget independent movie about a middle-aged loner facing down a terminal cancer diagnosis with his upstairs neighbor, debuted on Netflix on February 22nd, 2019. While most such movies focus on the patient’s experience, Paddleton is about cancer as a shared journey and a testament to the healing power of human companionship.

FAIR WARNING: if you haven’t seen the movie yet and want to avoid spoilers, stop reading now!

The film opens with Andy (Ray Romano) accompanying his friend Michael (Mark Duplass) to the doctor. There’s a tumor in Michael’s stomach and it’s already spread to his liver. The doctor’s recommending referral to an oncologist but won’t answer questions about prognosis.

Andy isn’t satisfied and pushes the issue on behalf of his friend. “How about this? How ‘bout I’m gonna make a statement, and if it’s a true statement you don’t have to correct me?” he asks the doctor, who’s obviously annoyed.

“Is what Michael has…incurable?”

“Dude, that’s a question. It has to be a statement,” deadpans Michael.

And that’s how it goes with the two of them. They take their liquor straight, and with a wry smile.

They’re an awkward but endearing couple – though they’re absotively posolutely not that kind of couple (as clearly spelled out in two awkward and hilarious scenes). They’re just neighbors. They just happen to have adjoining apartments…and spend most of their free time together, heating up frozen pizzas, watching Kung Fu movies, and playing a homegrown paddle-ball variant (which they call paddleton) in their every spare minute.

They’re something much more important.

Their relationship is uncomplicated and placid, because neither really likes to talk all that much. They don’t trouble each other with messy emotions. Michael is aloof about his cancer diagnosis -“It’s just meh” he says. He’s determined to maintain their normal routine as long as he can, and opt for physician-assisted suicide when he can’t.

It’s impossible not to love them, because they ask for very little and demand even less. We sense they both took a hard look at life a long time ago and came to terms with it in their own peculiar way.

The movie doesn’t condescend to them, or to us. There’re no epiphanies or dramatic gestures, nor is there a last-minute miracle. The end goes down just as Michael planned it. The story is simple, bordering on predictable. But yet we can’t stop watching these two oddballs fighting through the day as best they can.

The suspense comes from wondering how these two emotionally stunted people will handle something as devastating as death. And this is where Ray Romano really shines.

It’s beautifully painful to watch Romano’s face. He’s agonized to be there, watching his friend fade. It’s agonizing for him to bear witness. But he knows that not being there would be much worse. There’s never a moment of suspense about whether he’ll see his friendship through to the end. The suspense is in wondering what it’ll cost him.

Watching him, I couldn’t help wondering about what being involved in caring for the dying does – and maybe should – cost me.

Medical professionals involved in end-of-life care are often urged to “maintain healthy boundaries”. We’re not supposed to make the patient’s suffering our own, or mistake their family’s grief for our own – though in a very real way we never can. The patient is never our spouse/parent/sibling/child. The pain of losing a patient can never approach that level of personal loss no matter how much affection we’ve developed during our professional relationship. But yet we’re counseled to keep emotional distance.

It’s for our own mental health, we’re told.

And we cannot realistically sit 24/7 vigil with the dying. There simply isn’t the time. We have much work to do. And we cannot presume to take the seats of those whose grief takes primacy over our own.

But Paddleton reminded me how absolutely critical it is to stay with people emotionally at such times – no matter the cost.

Dying is sacred. There’s ritual and ceremony to it. And whatever the faith tradition, there’s a chalice brimming with grief that patients and their loved ones take turns drinking from. The cup is deep, and they need help getting to the bottom of it.

And I think we, as medical professionals, have to be willing to take a sip ourselves from time to time.

 

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.