Remembering Tamoxifen

By Margot Heffernan, MLS

Last week, I picked up a copy of the local paper. I took a cursory look at it, turning page after page, finding the usual, less than uplifting forecasts about the financial cliff, along side articles about chaos in Egypt, natural disasters, and accidental death. As I turned it over, letting the front page flutter out of my hands, and fall gracelessly, face down on the table top, I glanced down at the back page.  The headline, this headline, wasn’t like the rest. It resurrected a long stilled, but persistent memory, poignant and compelling:

Study: Longer Tamoxifen Use Cuts Breast Cancer Deaths

I ran my fingertips over the headline, pausing over the word, “tamoxifen”. I let my index finger dwell on that word for just a moment longer; I inhaled deeply, and read on.

The article summarized the important findings of one of the largest breast cancer trials of its kind- The Adjuvant Tamoxifen: Longer Against Shorter, aka, “ATLAS” trial, which began in 1996. Tamoxifen is the generic name for the first therapeutic agent that was given to women with hormone positive breast cancer. Also known under the trade names Nolvadex, Istubal, and Valodex, it has been the gold standard therapy for women (and men) with hormone driven breast cancer for thirty years.

ATLAS was a large multi-center study, involving 6,846 women with early stage breast cancer.  The aim was to determine whether it would be beneficial for women with hormone receptor positive breast cancer to take tamoxifen for ten years, rather than the standard and recommended five. 

This had been a big question in the breast cancer world for many years. The majority of breast cancers are “hormone positive”, meaning that either estrogen, and possibly progesterone, in some way fuels the tumor’s growth. Although hormone positivity tends to convey a less aggressive cancer than hormone negative disease, hormone positive breast cancer can recur much later. Sometimes it recurs up to ten, or even fifteen years after the initial diagnosis. Anti-hormone therapies, in the form of tamoxifen, or the newer generation of drugs known as aromatase inhibitors, have proven essential and lifesaving to a generation of women who might otherwise have died of their breast cancer. Through different mechanisms of action, these drugs “block” estrogen in the body, almost eliminating the source of nourishment for such tumors. Tamoxifen therapy is given after surgery, radiation, and/or chemotherapy;  the hope is that any residual cancer cells that are left circulating in the body will die, shut off from estrogen that generates their growth. Even so, a small, but significant percentage of these women will revisit their disease, sometimes long after five years of tamoxifen therapy ends.

The findings of the ATLAS trial, finally concluded after years of study, were nothing less than stunning: Extending tamoxifen therapy to ten years significantly improved a woman’s chances of surviving the disease.  Essentially, ten years are even better than five. Stunning, because previous studies had indicated just the opposite. In fact, researchers had cautioned against use of the drug beyond five years because it was believed that resistance to tamoxifen was inevitable: Tamoxifen resistance would render extended treatment essentially useless, and even, perhaps, detrimental to long-term survival.

I was caught off guard by this article, as I am usually on top of breaking medical news. Somehow, the ATLAS trial had escaped me. Learning about this in the paper was akin to a football fan discovering his team’s big win on the sports page the next morning. And this certainly was a big win. A big win for breast cancer patients, especially younger ones. (Younger, pre menopausal breast cancer victims are the primary beneficiaries of tamoxifen because the aromatase inhibitors are now exclusively used in post menopausal women.)  Even the acronym for the study – ATLAS – implied that this was huge, something that would resonate around the globe. Indeed, the women who were recruited to participate in this trial hailed from about three dozen countries.

Learning about this surprising reversal, though,  offered much more than an interesting discovery, or a novel finding reported from the trials of modern medicine. Intellect, cognition, reasoning, were now suspended, superseded by something visceral, emotive, and deeply stirring.

The threads of the tamoxifen article provided a haunting seque to the past-back to memories of my mother-steadfast trooper, tenacious fighter, unyielding in the face of her own breast cancer diagnosis. She was placid and stoic, an elegant survivor, long before breast cancer was a cause celebre. Evelyn was 72 years old when she was diagnosed in 1988. I was tormented and heartbroken. At thirty, I was a free spirit, but intricately attached to her, bound to her history, her essence, in an intimate and complex way. I would become her advocate- in- training; a one woman marching band, reveling in songs of hope only for her; an instigator of optimistic foresight.

Radical mastectomy was her treatment, followed by a five- year course of tamoxifen. Over the coming years, my mother spoke about her diagnosis in only the most oblique fashion. “Oh well”, she would say, ever so calmly, “Everyone has to have something.”

Doctor visits and assorted tests and scans became part of  the schematic of her life.  Cancer was something to be endured, like many of the other harsh and unpleasant vicissitudes of her days. If she were a direct and outspoken person, she might  have said, “Cancer, get in line. You’re not the only problem I have to contend with.” But it was not her style to talk back, not ever.

Even though she was found to have six positive lymph nodes, moving her up to a stage III breast cancer, her case was certainly not terminal. And so,  Evelyn took the tamoxifen religiously. She knew, and I knew, that here was something special, a gift from the gods of a modern-day pharmacopoeia. Unlike conventional chemotherapy, this was a pill that was taken daily, designed to hold off the vile and insidious creep of metastatic disease, perhaps forever, or maybe just for a while. And unlike chemotherapy, it was self-administered, a small pill taken just like blood pressure medicine. Just like diabetes medication. Just like the pills and tablets dispensed for the plethora of maladies deemed “controllable” by medical science. In other words, this cancer didn’t have to kill her, did it?

My mother had deeply felt the ravages of terminal cancer-her brothers, her mother, all eaten from the inside out by the relentless march of angry and merciless killer cells, invading and overtaking the internal landscape of the human body, organ by organ.  Tamoxifen provided comfort, perhaps the illusion, of a fate apart from such familiar suffering.  And just as my mother never referred to cancer by its name, neither did she utter the word “tamoxifen”. It was always “my pill”,” that tablet”, or “my medicine”.

“How ya feelin’?”, I would ask her, in my playful, lighthearted tone, not meant to invite a real appraisal of her condition.

“Oh, fine.” she would reply. “Just a little light-headed. Probably from that pill I take.”

And so it would go. “That pill” symbolized all of the morbid fears that my mother and I secretly harbored, but could never speak openly about. But tamoxifen was also magical and transformative, a bridge to the recent past, where we  could live as we did in those halcyon days before her cancer diagnosis. Here, we could imagine that this cancer, her cancer, had never existed. And maybe, just maybe, never would again.

Certainly, it seemed counterintuitive that a medication designed to prevent the spread of breast cancer should be discontinued after five years of therapy. But five years came and went. The tamoxifen experience was archived, along with so many other events, small and large, in a life long-lived.  My mother persevered, symptom free, a soldier at arms, in a war now at bay.

By 1998,  ten years had passed since her initial diagnosis. And now, a small dry cough appeared. Oh, and there was a little shortness of breath, she said, but really, it was nothing, she insisted.

In the end, of course, she would not be spared that dreaded fate, the one she must have sensed, coming, so close, like an eerie presence in the middle of a dark and private night.  My mother was taken, five years later, by breast cancer. It invaded her bones, her brain; it filled her lungs and viscera, and so many of the spaces in between.

Now, so many years from that place in time, I am humbled by the awesome and ironic twist of medical fortune. I am humiliated by the powerlessness of my own faith, the knowledge that she could not be spared that malignant and cruel death.

But mostly, I remember tamoxifen, once coveted and dear, still alluring and charismatic. Like an attachment felt, or a love once known, it haunts me still.