A Journey through Ma-Po Dofu

The other night, Marty and I decided we were in the mood for Chinese food. For some reason, I ordered a dish I haven’t had to date at our local Chinese restaurant—Ma-Po Dofu, sometimes also called, with the Japanese pronunciation, Ma-Po Tofu (the Ma-Po is short for “pockmarked grandmother”, which may describe how the dish sometimes looks). It is a Sichuanese dish, usually quite spicy, but is served all over Asia and in most Chinese restaurants in the U.S. as well.   I have to say I didn’t care for the version here—the tofu chunks were too large, and the sauce was not spicy enough and too heavy on the soy sauce.

This led me on a quest when I got home for the recipe I recalled from my graduate school days, from my fellow student and friend from Yale, Barbara Brooks. Barbara and I were in beginning Japanese class together in the Japanese Studies program at Yale—she did much better than me because she had already established some fluency in Chinese—and we became friends as well.   She was a good cook and because she was living with a Chinese roommate at the time, also had access to authentic Chinese style cooking.   Unfortunately, while I found a recipe in her handwriting for cheese balls (equally delicious, though not Chinese), I did not find the one for Ma-Po Dofu.

In the past several months since my diagnosis, I have reconnected with a number of old friends with whom I’d lost touch, and realized I had missed Barbara. We had last been in contact maybe 20 or more years ago, and I knew that she had gone on to get a Ph.D from Princeton, had married and had a daughter, and was teaching Japanese history at City College in New York. So I Googled her in the hope that I could locate an email address—and not only reconnect, but with the thought that perhaps she still had that great recipe for Ma-Po Dofu. To my shock and dismay, the first entry that appeared in my search was her obituary. She died at 60 more than three years ago—of metastatic breast cancer.

This hit me hard, not only because I regretted not contacting her before, but also because we had the same diagnosis. It led me to reminisce and find some pictures of the times we shared so many years ago, at Yale, in Japan, and even in Hong Kong. Some of those pictures—including the more serious one of Barbara posing for me at the Yale library (I was studying photography and developing my own film as a way of de-stressing from graduate school), are here. Who could have known then that we would share not only these good times, but the same fate in terms of the way we would leave the world?

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Yalies at my apartment in Japan. Barbara is second from the left, directly behind me.

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Barbara posing for me at the Yale Library.

Perhaps our most interesting adventure was my visit to her in Hong Kong, where her father and mother were stationed on a temporary basis.   Due to her father’s work, Barbara and her siblings grew up internationally, and she went to school in India and, if memory serves, Thailand as well. She showed me all over Hong Kong, and she cheerfully accompanied me by hydrofoil to Macao to the Temple of Kun Yam, which figures prominently in the opening paragraphs of my friend Warren Cohen’s history of Sino-American relations, America’s Response to China.   Here, in 1844, at the table pictured with the smiling Chinese man, the first treaty between the U.S. and China was signed. Barbara, with her fluency in both Japanese and Chinese, would go on to study and write about Sino-Japanese relations as well, making her own significant contributions to the understanding of East Asian diplomatic history. But in those days, we were two young women on a day’s adventure—as close to the then unrecognized People’s Republic of China as I would get until the early 1980s, when Warren and I made an advance trip for the governor of Michigan’s visit to Sichuan Province in preparation for the signing of a sister state agreement between Michigan and Sichuan (and though I don’t remember clearly, I’m sure I had some Ma-Po Dofu both in Hong Kong with Barbara and later in Sichuan).

I am both saddened by Barbara’s passing, and saddened that we share the same fate.  I guess we will meet again in the future–just not someplace in New York, but another venue altogether.

In other news, I am scheduled to start a new clinical trial at Mass General next week, or Plan E, as my doctor calls it (let’s hope the E stands for Effective).   I don’t technically meet all the qualifications for the trial—it is aimed at what’s called triple negative breast cancer, which means a complete absence of two hormonal markers and another marker called HER-2.   I am negative on two of the markers, but not the third. Nonetheless, my doctor and the study doctor felt that since the hormonal treatments have failed, I was a good candidate for this combo—it is a kind of Patriot Missile of therapies, as it delivers 200X the amount of drug to the cancer cells as IV chemo—and the study doctor was able to get me in. It will be somewhat harsher than the treatments I’ve had so far, but here’s hoping it also beats the cancer back more decisively.

“Shikata ga nai “ 仕方がない

During my lifetime, I lived a little more than 8 years outside the United States, all of it in Asia and Southeast Asia—Japan for more than four years, India for nearly three, and China for a little more than a year, where I also spent quite a bit of time in rural Korea.  I also worked for a Japanese company in the U.S. for 11 years, where I had many opportunities to interact with both the Japanese assignees and their families.   I have often wondered the impact that living in Asia and working with people from Eastern cultures has had on both my attitudes and approach to life—and death.

I was thinking about this more lately not only because of the latest setback in my treatment, but also because on our trans-coastal flight from San Francisco to New York in June, I watched a Japanese film called “Hana-chan no Misoshiru” (Hana’s Miso Soup). It is based on a true story, and is about a young woman diagnosed with breast cancer shortly before her wedding, who then goes on to have a child, which is risky because it can cause recurrence. Indeed, several months after her daughter’s birth, the cancer does return and is metastatic.   Although she is able to beat it back temporarily with more chemotherapy, eventually the disease progresses to the point where nothing more can be done. Wanting her 4 year old daughter to learn how to be self-sufficient, she teaches her how to cook, including how to make miso soup, a staple of Japanese cuisine—hence the movie’s title.

Throughout this ordeal, Chie, the mother, refuses to be a victim, understanding that her cancer may return if she goes through with the pregnancy, and later, that she is likely to die while her daughter is still a small child. While being proactive about treatment and her diet, she also accepts her fate without rancor or anger.

Which brings me to the title of this post—shikata ga nai (or sometimes, shou ga nai). Literally, it means, “there is no way,” or more colloquially, “it can’t be helped.”  I probably heard this phrase at least daily when I lived in Japan, applied to all sorts of situations—from a traffic jam in Tokyo to an earthquake to someone’s death, all of which were events that were not in an individual’s control.   Certainly it has come to my mind often when I think about having cancer.  Sometimes misinterpreted as passivity, “shikata ga nai” doesn’t really dictate that you do nothing—as Chie in the film demonstrates. It does mean an acceptance of the circumstances you have been dealt, without anger or self-pity.

I vividly recall a situation when I was working for Mazda that illustrates this latter point. I was interpreting a media interview for the then new President of the manufacturing company, who did not speak much English. He had been born and raised in Hiroshima, and was a small boy at the time of the dropping of the first atomic bomb.   Because Hiroshima was viewed as a target towards the end of the war, he, his mother and siblings had relocated to a nearby area in the country, but his father continued to work in the city.   The father, like so many others, was killed in the bomb that was dropped on August 6, 1945.   The reporter was very curious about my boss’s reaction to this, especially since he was now living and working in America. He wanted to know if he “resented” America or Americans or had been “angry” that he lost his father due to the bombing—certainly there were many in Flat Rock, Michigan, including the city’s mayor (who had a statue of Iwo Jima in his office) who had a hard time getting past the Japanese being our enemy in World War II. My boss replied simply, “No”—and used that well worn phrase, “shikata ga nai.” Then he added something I have never forgotten: “I was of course very sad that my father had died. But I was also grateful that my mother and my siblings still lived.”

I am not sure the degree to which this mentality—of acceptance of the things not in one’s control, without being consumed by anger and resentment—has penetrated my consciousness. I suspect it has to some degree.  It is balanced—as it is in Japanese society as well–by another well known phrase, “gambaru”—to persevere, or to slog on through tough times.   This Sunday’s New York Times magazine contained what may be viewed as an extreme example of that—the man who has been on more than 100 scuba dives in the attempt to locate the body of his wife, who died in the Sendai tsunami. Acceptance tempered with perseverance—it seems like a good formula.

 

Scans and “Scanxiety”

Metastatic cancer patients, regardless of the type of cancer they have, quickly become used to the routine of “scan, treat, repeat.” On some interval, usually 3 months, you have CT, bone, and/ or PET scans that show whether a drug regimen is working. If it is (or if the results are stable), you continue until the cancer starts growing again. If not—you move on to something else, for as long as something else acceptable is available and tolerable. The time around these scans is usually quite nerve-wracking—hence the made up word known as “scanxiety.”

Last week I had a brain scan and a CT scan. The brain scan showed that the radiation worked on the areas treated, and the tiny seeds in the brain itself, not in a place at the moment to cause symptoms, grew slightly. The CT scan, however, showed definitively that the drug I am currently on is not working—the spots on my liver, in particular, got larger. So I am off that drug, an oral chemotherapy, and am waiting to hear what is next—one of two clinical trials, or possibly another chemotherapy. (One of the trials involves immunotherapy, which has been successful in other forms of cancer –especially melanoma–and is now the subject of a number of trials in breast cancer as well. )

I have now had a total of eight series of scans since my diagnosis of metastatic breast cancer, and all but two have involved bad news. I have not been one of those people who hear that their cancer has shrunk dramatically, or has become invisible on the scan (No evidence of disease—doesn’t mean there is no cancer, but that it can’t be picked up on a scan).  Rather, each new drug regimen usually fails, increasingly by the first set of scans.

On some level, I realized the other day that while I’m not particularly fatalistic, I have now come to almost expect this.    The news, however disappointing it is to hear at the time, doesn’t hit me quite as hard as it did earlier in the process. The only positive in my case is that the cancer, though obviously very wily (since I go to Mass General, I joke that my cancer is so smart it got into Harvard…..) is also not particularly fast growing—for example, my liver lesions grew by only about a centimeter over more than a three month period, and the lymph nodes by much less than that. I also had a harder time on this particular drug than on previous combinations, so in a way I’m not sorry to move on.

Still, it is increasingly hard to approach the “next thing” with the same optimism I felt a year ago. Fortunately, I still feel relatively well and have options left—that’s one of the advantages of being at a state of the art center such as Mass General–but obviously, the opening is narrowing. The conventional wisdom is that as the cancer continues to morph, each treatment generally has a lower percentage chance of working than those that come before. This does not mean that the next thing can’t work, but the fact that I have cycled through so many treatments in such a short period of time is objectively not a good sign.

My main goal at the moment is to stay in balance—to neither fall into despair, nor have unrealistic hope. Probably the most difficult thing to deal with is the fact that no matter what I do, I am ultimately not in control what happens with the cancer. I am only in control of how I choose to respond to it. In a future post, I want to write about the influence of living in Asia on my reactions, as I’ve increasingly realized the degree to which I have absorbed, albeit unconsciously, a certain acceptance of the great uncertainty of life.  And so, I move on to the next thing.

The Humans

Last night, my husband and sister-in-law and I saw the Broadway play, “The Humans.”  It is set around a Thanksgiving dinner and tells the story of an average family dealing with an aging parent and dementia, a broken relationship, chronic illness, weight issues, job loss, money troubles, and a painful, life altering secret.  It also has moments of grace–the obvious love of the family members for each other, a near miss in getting caught in the 9/11 tragedy, and the fact that to a person, the characters have retained a sense of humor despite life’s troubles.

The theatre was packed and we even had a celebrity siting–the actress Nicole Kidman came in a few minutes after we did and was seated several rows ahead of us.  As I looked around, it occurred to me that the very fact that we could afford to enjoy this play puts us in a very privileged position.  A night’s entertainment on Broadway these days for three people is  easily the cost of a car payment, a new dishwasher, or a medical co-pay for a family not unlike those profiled in the play.  The same is true, these days, of a night out at a Major League baseball game–once a simple and affordable pleasure for even a working class family, it is no longer accessible to many.

This struck me in part because a couple of weeks ago, I got together with an old friend I hadn’t seen for many years, and she reminded me that when we both worked for state government back in Michigan 30 years ago, we once flew to New York for a weekend Broadway blitz–we saw four or five plays, both on and off Broadway.  Such an undertaking now would give pause at a minimum, and probably be unaffordable for the average state worker.

The play itself contains a brief discussion, almost in passing, of the divide between the wealthy and the poor, and the degree to which greed has become a disease.  This is not a political post, but despite my thorough enjoyment of the play,  it also served as one more piece of evidence of how far we have strayed as a society.

 

Clinical Trials

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Since I was diagnosed with metastatic breast cancer a year and a half ago, I have been on four clinical trials. In fact, the only treatment I’ve had that hasn’t been trial based is the one I’m on now, an oral chemotherapy called Xeloda.  Although I’ve had mixed success personally with trials, I’m a big fan of them and encourage anyone with a challenging disease like cancer, heart disease, Parkinson’s, Alzheimer’s, or others, to check out what’s available on https://clinicaltrials.gov and to ask your doctor.

What is a clinical trial?  Clinical trials study both drugs and other modalities to determine safety and efficacy in humans, and whether or not a particular treatment is superior to what may already be on the market and approved by the relevant government agency (in the case of the U.S., that’s the FDA).   Trials may be for healthy people or for those with a particular disease. For metastatic breast cancer, for example, there are currently more than 700 trials around the world studying various therapies. Some of these are particular to breast cancer, but increasingly, trials are open to more than one kind of cancer, sometimes termed “basket studies.” This is because a particular mutation may occur in more than one type of cancer, and a targeted therapy could address it.

Trials come, generally, in three phases (a fourth phase is sometimes added after a therapy is commercially available).  Phase I is the most experimental as a drug, for example, has not yet been studied in humans. Phase I trials involve a fairly small number of people; different participants will be given different dosages to measure safety, side effects, and efficacy, as well as how a drug is absorbed in the system.   Gradually, this process is refined, and a more mature Phase I trial—I’ve been on two of these—has more participants, although the administration may still vary according to which “arm” of the trial you are in.   Phase II is an expansion of Phase I, where even more participants are enrolled. Finally, Phase III compares the study protocol or drug to an established alternative. In Phase III, you are randomized either to the standard protocol or the new alternative.

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My first trial was a Phase III trial at Dartmouth, and I was randomized to the study drug, a marine based chemotherapy developed in Japan, called eribulin. This lasted about 5 months before the cancer began growing again, and I was removed from the trial.  My second trial was a genomic test, administered out of Ohio State’s James Cancer Center, that identified mutations in my cancer that might be receptive to therapies. (The advantage of this trial was that the test was free, whereas having it done commercially would have been several thousand dollars, probably not reimbursed at that time by insurance.) My third and fourth trials were at Mass General, and both involved a combination of new, not yet on the market targeted drugs, and others that had shown efficacy.   Unfortunately, none of these worked for long in my case (my doctor said they have all “underperformed” relative to expectations), but I have some comfort in knowing that my participation is advancing understanding of new therapies for other patients.

There are advantages and disadvantages to trials.   The main advantage is that you are often (with the exception of Phase III trials when you are randomized to a standard therapy), getting the latest available scientific thinking—you have access to therapies that otherwise are not yet available. A second advantage is that you get very personalized treatment—trial nurses are assigned to each participant, and I have found them, without exception, fantastic to deal with and very proactive.

There are disadvantages, however.  One is time. Often, especially in the earlier phases, you will be subjected to numerous blood draws and tests to determine how the drug is being absorbed (the record for me was 16 vials), sometimes with fasting and sometimes not. As you progress in the trial, these interventions become less frequent, but the schedule of treatment is often quite strict—on the Japanese-sponsored trial I was on, I had to cancel a planned international trip because it fell during a week I was scheduled for treatment, and the only exception allowed was if I had had a medical reason (e.g. low white blood cell counts).   Secondly, trials can be quite strict on who they admit. This includes thresholds on certain blood levels, such as liver enzymes, white cell counts, and even mineral levels such as calcium, phosphorus, and potassium, as well as previous therapies (there is often a limit, for example, on the number of previous chemotherapies that you can have to be a participant in certain trials).   In my case, now that I have brain metastases, a number of trials for which I would otherwise be eligible are off limits as many therapies do not cross the blood-brain barrier.   Guidelines for continuing are also strict–the last trial I was on worked on some of my cancer, but I had a new lesion in my liver, so had to be removed from the trial as any new lesion is generally disqualifying.    Finally, I’ve found that as a patient, you have to do a fair amount of your own research, as institutions generally are aware of and promote only their own trials.   Research is how I found the genomic testing at the James Cancer Center, for example.

I am lucky in that I am near some world premier institutions, all NCI designated cancer centers, including Dartmouth and Mass General, where I’ve had treatment, as well as Dana Farber (and Memorial Sloan Kettering is not that far).   These research hospitals tend to be where the bulk of trials take place, but smaller centers get in on the action as well, especially for Phase III trials.   Having said this, many trials fail to enroll enough participants, and part of the reason for this is knowledge and access—I think some may fear they are being used as human lab rats– but also the complexity of participation. Despite the fact that I’ve already been on trials and the future options may be more limited, I remain committed to participation both for its potential benefits for me personally, and to advance the cause of better treatment for others.

 

 

Metastatic Breast Cancer–the Ugly Stepsister

Before I was diagnosed with metastatic breast cancer (MBC), I confess that I didn’t know much about it. I assumed, as many probably do, that Stage IV breast cancer occurred primarily among people who hadn’t caught the disease early.   There was the very public example of Elizabeth Edwards, whose initial tumor was a whopping 9 centimeters, and who then faced a metastatic recurrence—and eventual death—a few years later.   And, like many, I suppose I had drunk a bit of the pink Koolade that “early detection” is key—that lives are saved when women get mammograms, their tumors are small and haven’t spread, etc. Since I fell into this category, I certainly thought—and hoped—that I was among them.

The facts are quite different. The incidence of de novo Stage IV, or metastatic, breast cancer is very small, less than 10%. The remainder of cases come from women like myself, many of whom got regular mammograms, were diagnosed with early stage disease and then had a recurrence. (It should be noted that there is NO effective screening tool for women under 40—mammograms have limited utility in younger women who have denser breast tissue than their older counterparts). Up to 30% of women with early stage disease, in fact, will go on to develop metastatic cancer, sometimes many years later—and this includes women who had Stage 1 or even Stage 0.    Because so little money goes into research for a cure (only 7% of research dollars in the U.S. and U.K. go to metastatic disease, the only kind that kills) scientists simply do not understand yet why—despite treatment– the cancer lays dormant, sometimes for a decade or more, and then recurs elsewhere in the body. The bottom line, scary as it is for women who have had early stage disease, is that at this time, you simply cannot know if you are part of the 70% majority or the 30% minority.

Statistically, we don’t even know how many women and men are living with metastatic breast cancer, because data is only tracked on the original diagnosis. Estimates put the number in the United States at about 150,000, but when a metastatic breast cancer patient dies, their original diagnosis—in my case Stage IIA—follows them.

Because of all the hype about mammograms and early detection, the focus especially in the United States—and more importantly, the funding– over the last thirty or more years has been on awareness and on ensuring that women get screened. This is not to say that mammograms and self exams do not have their place—they do. But to imply that they have improved survival is simply false. The same number of women (and a few men) are still dying of this disease as they did 40 years ago—40,000 per year, or 108 every single day.

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Partly for this reason, you will not find many fans of the Komen Foundation, the ultimate pink juggernaut, among those who have metastatic disease. Despite the fact that Susan Komen herself died of metastatic breast cancer, the cruel myth has been perpetrated by the Komen Foundation that survival rests in the hands of the patient, through early detection. According to one Komen ad, “What’s the key to surviving breast cancer? It’s you.”—the clear implication being that if you get metastatic disease, it’s your own fault.    As noted above, fewer than 10% of women are initially diagnosed with Stage IV (which has a 23% five year survival rate), the rest—assuming they are of an age when a mammogram is even a useful tool—may still face a recurrence even if they have been diligent about screening.  Komen has generally minimized any publicity of Stage IV or metastatic disease patients during Breast Cancer Awareness month, instead choosing to focus on the “feel good” message of early detection and cure, replete with dogs dressed in pink bras.

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A recent report on the global status of MBC (Advanced) concludes that research on metastatic breast cancer has not kept pace with advances in other forms of cancer, such as melanoma and lung cancer.   The report recommends a much more aggressive approach to investigating the genomic underpinnings and improvement of outcomes in metastatic disease.  Organizations such as Metavivor and the Breast Cancer Research Foundation spend the bulk of their donations on research into metastatic disease, and are, in my opinion, a much better investment than Komen and their pink dogs with bras.  If this is a cause that speaks to you, I encourage you to check them out.

Across this Land

2016-06-21 18.49.55I have relatively few items on my bucket list, but traveling by train across the United States was one of them. When I was 5 or 6, my grandparents took the California Zephyr from Chicago’s Union Station to San Francisco. I remember being fascinated by the letters and postcards they sent along the way, as well as the exotic gifts they brought me from California– including a pair of blue Chinese-style silk pajamas which might have been my first exposure to anything Asian.  My dad also loved train travel and his highest compliment for a cup of coffee in a restaurant was that it tasted like “dining car coffee,” a reference to the exquisite meals that used to be served aboard trains in the United States.

2016-06-22 06.49.32Although I had taken the Empire Builder from Chicago to Seattle once a long time ago, I had never traveled the entire length of the U.S. from New York to California.   So, this past week, Marty and I boarded the Cardinal, which runs from New York to Chicago via the Smoky Mountains, and then the Zephyr from Chicago.   Altogether, the trip took three nights and four days.

2016-06-21 12.47.27The scenery along both routes is both beautiful and informative—the majesty of the Smoky and Rocky mountains, the grandeur of the Colorado River, the eerie Ruby Canyon which is reminiscent of the Grand Canyon, and miles and miles of industrial corn fields and ethanol production facilities on the heartland stretch, as well as orchards and occasional wind farms when you reach California.  The train riders included a wide variety of people, from families to international travelers, who, like us, wanted to experience the full length of the United States from the ground.

2016-06-21 09.38.52The conditions of travel, however, are not those of former days. This was no surprise to me as I have often traveled by train since moving to the east coast, and am familiar with both the equipment breakdowns and delays associated with Amtrak (both of which occurred on this trip, as well).  Overnight travel poses additional challenges as the sleeper car rooms –even the largest ones–are about the third the size of a cruise ship cabin, and don’t allow for much maneuvering, and parts of the track, especially on the Cardinal, are quite rough (the Zephyr route is much smoother, especially through the western states) leading to disturbed sleep.  In addition, because of the extreme heat in the west, there were stretches where the train could only go 15 miles per hour due to the expansion of the tracks and safety concerns. The food is not bad, although certainly far from the service and ambience provided in my parents’ and grandparents’ era.   For part of the trip, likely because of the medication I’m on, I was also not feeling that well, which didn’t help. Despite the beautiful scenery, the hot shower and comfortable bed that awaited us in San Francisco were most welcome.