Arsenic: New TNBC Treatment?

Arsenic trioxide combined with nanotechnology might provide the double whammy that can fight triple negative breast cancers, say researchers at Northwestern University. Arsenic has been effective against blood cancers but not against solid tumors because it flushes through the blood stream too quickly. An arsenic nanoparticle, however, was successful in targeting TNBC in mice, causing cancer cells to die. Read more at Genetic Engineering and Biotechnology News.

Can TNBC cells be reprogrammed to respond to tamoxifen?

FROM A NEWS RELEASE FROM THE SAMUEL WASMAN CANCER RESEARCH FOUNDATION:

Research on breast cancer cells may create new treatment for triple-negative breast cancer.

Using a small molecule decoy, investigators funded by the Samuel Waxman Cancer Research Foundation have managed to block protein interactions and induce epigenetic reprogramming in human and mouse breast cancer cells, essentially changing the gene expression of breast cancer cells to behave in a more normal manner. The research illustrates what may perhaps become an effective targeted epigenetic therapy in breast cancer. Interestingly, the targeted treatment showed exciting results in triple-negative breast cancer cells, reverting their function and appearance, and sensitizing them to tamoxifen and retinoids.

By introducing a small peptide, called the SID decoy, to interfere with protein binding in the Sin 3 PAH2 domain, scientists reduced the growth of triple-negative cancer cells by 80 percent. The decoy also blocked cancer cell invasion, which may shed light on preventing metastasis. The study was published in the June 29 print edition of the journal of the Proceedings of the National Academy of Sciences.

Triple-negative breast cancer is an aggressive form of breast cancer more commonly diagnosed in young women, African-American women and women with BRCA-1 mutated cancers, said medical oncologist Samuel Waxman, M.D., the study's senior author. Currently, the only treatment options that women with triple-negative breast cancer have are radiation therapy, surgery and chemotherapy. Women with triple-negative breast cancer do not respond to hormonal therapy or Herceptin and have a higher recurrence rate after chemotherapy.

"Hopefully, this breakthrough research means we can expand treatment options for women with triple-negative breast cancer and give them a chance at anti-estrogen hormonal therapy," said Dr. Waxman, a professor in the department of Hematology and Oncology at Mount Sinai Medical Center in New York City and the scientific director of the Samuel Waxman Cancer Research Foundation.

Arthur Zelent, Ph.D., a co-author of the study, said researchers plan to investigate small molecules that are predicted to have the same effect as the decoy peptide. "This could form the basis for a new class of targeted, epigenetic drugs in breast cancer," said Dr. Zelent, a team leader at The Institute of Cancer Research in the United Kingdom.

Elizabeth Woolfe, the executive director of the Triple Negative Breast Cancer Foundation, said though the study's results are too preliminary to make a clinical impact for cancer survivors today, she added, "The findings offer encouraging results that could lead to other promising research and the potential for new therapeutics for women facing triple-negative breast cancer."

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About the Samuel Waxman Cancer Research Foundation

The Samuel Waxman Cancer Research Foundation is an international organization dedicated to curing and preventing cancer. The Foundation is a pioneer in cancer research, focusing on uncovering the causes of cancer and reprogramming cancer cells.

We dedicate ourselves to delivering tailored, minimally toxic treatments to patients. Our mission is to eradicate cancer by bridging the gap between lab science and the patient.

Through our collaborative group of world-class scientists, the Institute Without Walls, investigators share information and tools to speed the pace of cancer research. Since its inception in 1976, the SWCRF has awarded more than $70 million to support the work of more than 170 researchers across three continents.

For more information, visit the Waxman center.

Another Healthy Breakfast

A few months ago I posted information on my favorite breakfast smoothie. I am now trying a different approach, for a little variation. (Also because my cholesterol was a tad high.)

Here's my new favorite:

Blueberries coated with flax seed and yogurt. It's easy. Just get some frozen berries--they are cheaper than fresh and every bit as healthy, if not more so. Put 1/4 cup in a bowl and top with 2 tablespoons of ground flax seed. Mix thoroughly--the seed will naturally adhere to the frozen berries. Then add 1/2 cup of fat-free plain yogurt. This is packed with antioxidants and gives you a nice bump of calcium as well. I have this as my "breakfast appetizer"--what I have when I first wake up. (Make sure you use ground flax seed, as whole seeds just go right through you. And, once they are ground, store in the refrigerator.)

I follow that, in an hour or two, with oatmeal--1/2 cup of whole oats in 1 cup of water. Then I mix another 1/4 cup of blueberries in. This lowers the cholesterol and adds a few more antioxidants.

I usually go for a walk between the two. We are now at our Colorado cabin, so we go for a healthy hike.

NKYR-102 May Help Women with TNBC Metastatic Breast

FROM THE PR NEWSWIRE: New drug may improve response for women whose tumors have not responded to taxanes.

SAN CARLOS, Calif., June 9 /PRNewswire-FirstCall/ -- Nektar Therapeutics (Nasdaq: NKTR) today announced positive preliminary initial results from a two-stage Phase 2 clinical study evaluating single-agent NKTR-102 in women with advanced/metastatic breast cancer patients who have received a prior taxane. The increased use of taxanes in breast cancer often renders tumors resistant to these drugs by the time the disease recurs, thereby underscoring the urgent need for new treatment options with novel mechanisms of action for metastatic disease.

The single-agent NKTR-102 study recently completed enrollment with a total of 70 patients with metastatic breast cancer. A significant majority of the women had been treated with prior anthracycline/taxane with or without capecitabine. Of the 70 patients, 66 patients are currently evaluable per RECIST for the imaging-based primary endpoint of objective response rate. Confirmed and unconfirmed RECIST responses were 21% (14/66) overall for single-agent NKTR-102, with 18% (6/33) for the q14d dose regimen and 24% (8/33) for the q21d dose regimen. There are a significant number of patients in the study still on therapy with NKTR-102.

"This is a very promising result in patients with metastatic breast cancer who have failed prior taxanes and in most cases, prior anthracyclines," said Prof. Ahmad Awada, Head of the Gynecologic Oncology Clinic at the Institut Jules Bordet in Brussels, Belgium. "I have patients who have not responded to any prior therapy but who have experienced a good response to NKTR-102. These data are quite encouraging, and NKTR-102 should be taken forward as a single agent and in combination therapy in patients with difficult-to-treat disease such as triple-negative breast cancer and anthracycline/taxane failures."

Of the 70 patients enrolled in the study, approximately 85% had received prior anthracycline/ taxane, either with or without capecitabine therapy. The drug has been well-tolerated to-date. The most commonly observed grade 3 or grade 4 side effects in the study to date (every 14 day/every 21 day dose schedule) were diarrhea (14%/6%) and neutropenia (9%/6%). There were low rates of alopecia observed with single-agent NKTR-102, with only a small number of women experiencing Grade 2 alopecia.

"We are highly encouraged by the compelling preliminary activity observed to-date in the patients from our study," said Lorianne Masuoka, M.D., Senior Vice President and Chief Medical Officer. "This, combined with our recent results presented at the 2010 ASCO meeting for single-agent NKTR-102 in women with platinum-resistant and refractory ovarian cancer, make us very excited about the future of NKTR-102 as a novel anti-cancer agent."

About the Study

The Phase 2 study is evaluating two dose regimens (q14 day and q21 day) of single-agent NKTR-102 in women with metastatic breast cancer. The study employs a two-stage design, with 40 patients in the first stage and 30 patients in the second stage. Secondary endpoints of the Phase 2 study include progression-free survival and safety.

About Metastatic Breast Cancer

Breast cancer is one of the most common cancers among every major ethnic group of women in the United States. The chance of developing invasive breast cancer at some time in a woman's life is a little less than 1 in 8 (12%). According to the American Cancer Society, nearly 200,000 new cases of invasive breast cancer were diagnosed in women in 2009. Anthracyclines and taxanes are the most active and widely used chemotherapeutic agents for breast cancer, but the increased use of these agents at an early stage of disease often renders tumors resistant to these drugs by the time the disease recurs, thereby reducing the number of treatment options for metastatic disease. Drugs used to treat patients who progress following AT treatment can be as high as 20-30%; however, resistance develops rapidly and new agents with different mechanisms of action, such as topoisomerase I-inhibitors, are needed to allow novel ways to overcome the problem of drug resistance.(1) There are currently no FDA-approved topoisomerase-I inhibitors to treat breast cancer.

About NKTR-102

Nektar is developing NKTR-102, a topoisomerase I inhibitor-polymer conjugate with reduced peak concentrations and a continuous concentration profile. NKTR-102 was invented by Nektar using its advanced polymer conjugate technology platform, and is the first oncology product candidate to leverage Nektar's releasable polymer technology platform.

In addition to the fully-enrolled Phase 2 studies in platinum-resistant ovarian cancer and metastatic breast cancer, NKTR-102 is also being tested in a separate Phase 2 clinical trial in patients with second-line colorectal cancer and a Phase 1 clinical trial of NKTR-102 evaluating it in combination with 5-FU therapy.

PEM Scanners May Be Better at Spotting TNBC Tumors

From the PR Newswire

SAN DIEGO, June 18 /PRNewswire/ -- Naviscan's Positron Emission Mammography (PEM) technology was the focus of several presentations and discussions at the Society of Nuclear Medicine Annual Meeting in Salt Lake City. The focus represents a growing interest and validation of how PEM can play an important role in the fight against breast cancer.

PEM scanners are high-resolution breast PET systems that can show the location as well as the metabolic phase of a lesion. This information is critical in determining whether a lesion is malignant and influences the course of treatment. Other imaging systems, such as mammography and ultrasound, show only the location, not the metabolic phase. PEM scanners, which are about the size of an ultrasound system, are manufactured by Naviscan, Inc. and have been commercially available since 2007.

A presentation with considerable attention was of the release of the findings from the NIH-sponsored clinical study comparing PEM with breast MRI. This multi-site study (NIH Grant 5R44CA103102) of hundreds of women with newly diagnosed breast cancer shows that PEM may reduce unnecessary breast biopsies. The study found that PEM was significantly more precise at identifying benign and cancerous lesions, in what scientists call "Positive Predictive Value" or "PPV," therefore reducing the number of unnecessary biopsies.

Other presentations on PEM were led by leading researchers from M.D. Anderson Cancer Center, Johns Hopkins, Swedish Cancer Institute, University of Washington and Boston University. These presentations covered not only the clinical advantages of PEM today, but also exciting new areas of focus.

The triple negative cancer study results were particularly welcomed news. The study enrolled 281 patients with newly diagnosed breast cancer and the results suggested that PEM may be able to properly characterize triple negative tumors. Triple negative breast cancers make up between 13-38% of all breast cancers and are the most difficult to treat because they are so aggressive.

New drug improves overall survival of women with metastatic TNBC

From a News Release from Eisai Oncology

CHICAGO--(BUSINESS WIRE)--Results of a Phase III study presented today at the American Society of Clinical Oncology (ASCO) Annual Meeting showed that Eisai’s eribulin mesylate significantly improved median overall survival (OS) compared with Treatment of Physician’s Choice (TPC) in heavily pre-treated metastatic breast cancer patients.

These results were presented as part of an ASCO-sponsored press briefing; additional details from the study will be presented in an oral session on June 8, 2010 at 9:30 a.m. in East Hall D1 at Chicago's McCormick Place. The study abstract has also been selected for presentation at the 2010 Best of ASCO® Meetings, which will be held in San Francisco and Boston in the United States and in several countries around the world in the months following the ASCO Annual Meeting.

The Phase III “EMBRACE” study (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice Versus Eribulin E7389) met its primary endpoint of overall survival, showing that patients who received eribulin survived a median of 2.5 months longer than patients who received TPC (overall survival of 13.12 months versus 10.65 months, respectively, p=0.04). Results from EMBRACE also showed that a secondary endpoint of overall response rate (ORR) was statistically significant. Another secondary endpoint, progression free survival (PFS), was supportive of the primary endpoint but did not reach statistical significance.

“To date, no single-agent Phase III clinical trial has demonstrated improved survival in women with heavily pre-treated metastatic breast cancer,” said Chris Twelves, M.D., lead investigator for the EMBRACE study and Professor of Clinical Cancer Pharmacology and Oncology from the University of Leeds and St. James’s University Hospital, Leeds, United Kingdom. “These results showed that eribulin significantly improved overall survival versus a variety of agents used in a real-world setting, which previously no single agent has shown.”

The most frequently reported adverse events (AEs) among patients treated with eribulin were asthenia, or fatigue (53.7%), neutropenia, or low white blood cell counts (51.7%), alopecia, or hair loss (44.5%) and peripheral neuropathy, or numbness and tingling in different parts of the body (34.6%). Treatment-emergent serious AEs were reported for 25 percent of patients in the eribulin group and 25.9 percent of patients in the TPC arm.

About the Study

EMBRACE was an open-label, randomized, multi-center study of 762 patients with locally recurrent or metastatic breast cancer who were previously treated with at least two and a maximum of five prior chemotherapies (≥2 for advanced disease), including an anthracycline and a taxane. Patients must have been refractory to the most recent chemotherapy, documented by progression on or within six months of therapy. The study was designed to compare overall survival in patients treated with eribulin versus a TPC arm, reflecting a real-world clinical setting where a variety of agents are used to treat patients with advanced breast cancer.

Patients were randomized in a two-to-one ratio to receive either eribulin (1.4 mg/m² administered intravenously for two-to-five minutes on days 1 and 8 of a 21-day treatment cycle) or TPC. TPC was defined as any single agent chemotherapy, hormonal treatment or biological therapy approved for the treatment of cancer; or palliative radiotherapy administered according to local practice. The median age of study participants was 55 (range 27-85); 16 percent of patients had HER2 positive breast cancer and 19 percent had breast cancer that was negative for estrogen, progesterone and HER2 receptors (triple-negative breast cancer).

About Metastatic Breast Cancer

Worldwide, more than one million women a year are diagnosed with breast cancer. Approximately 50 percent of women worldwide initially diagnosed with breast cancer are expected to develop recurrent or metastatic disease within 15 years of their first diagnosis. Only one in five women with metastatic breast cancer survives longer than five years. In the United States, an estimated 155,000 women are currently living with metastatic breast cancer, and that number is projected to increase to 162,000 by 2011.

“Women with advanced breast cancer are in critical need of new treatment options,” said Alton Kremer, M.D., Ph.D, Global Head of Clinical Development for Oncology at Eisai Inc. “In this study, eribulin has shown an improvement in survival, and if approved by health authorities, it may offer patients a new treatment option at this stage of the disease.”

About Eribulin

Eribulin mesylate (E7389) is an investigational agent being evaluated as a potential treatment for locally advanced or metastatic breast cancer. A non-taxane, microtubule dynamics inhibitor, eribulin is a synthetic analog of halichondrin B, which is derived from a natural product isolated from the marine sponge Halichondria okadai.

On March 30, 2010, Eisai announced it had submitted simultaneous regulatory applications for approval of eribulin mesylate for the treatment of locally advanced or metastatic breast cancer to agencies in Japan, the United States and the European Union (EU). The eribulin New Drug Application (NDA) was granted priority review status by the U.S. Food and Drug Administration (FDA) on May 28, 2010.

Eisai Oncology

Eisai Oncology is dedicated to discovering, developing and producing innovative oncology therapies that can make a difference and impact the lives of patients and their families. This passion for people is part of Eisai’s human health care (hhc) mission, which strives for better understanding of the needs of patients and their families to increase the benefits health care provides. Our commitment to meaningful progress in oncology research, built on scientific expertise, is supported by a global capability to conduct discovery and preclinical research, and develop small molecules, therapeutic vaccines, biologic and supportive care agents for cancer across multiple indications.

Radiation after mastectomy increases survival, reduces risk of recurrence

Women with estrogen-negative breast cancer who received radiation after a mastectomy lowered their recurrence risk by 30 percent and increased their five-year survival by 50 percent. Those who especially benefitted from post-mastectomy radiation were younger than 40 years old; had high nuclear grade, estrogen-negative tumors status; and had cancer that had spread to their lymph nodes. This according to research published in the International Journal of Radiation Oncology.

Can genomic cancer sequencing guide TNBC treatment?

FROM A NEWS RELEASE FROM LIFE TECHNOLOGIES CORPORATION

CARLSBAD, Calif. - (Business Wire) Life Technologies Corporation today announced the creation of the Genomic Cancer Care Alliance to help people battling cancer gain access to treatment options found through analysis of their genomic information. Founding partners include Fox Chase Cancer Center, Scripps Genomic Medicine, and the Translational Genomics Research Institute (TGen).The announcement came during the Consumer Genetics Conference being held June 2-4 in Boston.

The Alliance will launch a pilot study aimed at determining whether whole-genome sequencing can better guide treatment decisions across a number of difficult-to-treat cancers. US Oncology, Inc., the nation’s leading integrated oncology company, is expected to serve as the contract research and site management organization for the study.

The study builds upon a research trial announced earlier this year by Life Technologies, TGen and US Oncology to sequence the genomes of 14 patients diagnosed with triple negative breast cancer whose tumors have progressed despite multiple other therapies. In contrast to the breast cancer trial, this study is the first one to evaluate the use of whole-genome sequencing information in guiding treatment decisions across a wide range of cancer types.

“This is a groundbreaking initiative for oncologists and their patients that should demonstrate how whole-genome sequencing with analytics and counseling can identify a treatment plan customized specifically for each seriously ill patient,” said Paul Billings, M.D., Ph.D., the Alliance’s Chief Medical Officer, and a thought leader for more than 30 years in the application of genetics in medicine, who currently serves as Director and Chief Scientific Officer of the Genomic Medicine Institute at El Camino Hospital. “There is an urgent need to define and validate a complete medical workflow for genomic-based cancer care.”

The Alliance expects the study to begin enrolling patients late this year. Protocols for the study are currently being developed and will most likely focus on advanced cancer patients who have failed initial rounds of therapy.

“Life Technologies is proud to be leading this initiative with a number of dedicated institutions who are committed to and believe in the clinical utility of cancer sequencing,” said Gregory T. Lucier, Chairman and Chief Executive Officer of Life Technologies. “We strongly believe that genome sequencing will allow physicians to treat their patients not just based on the type of cancer they have, but on the biological pathways that led to mutations, which ultimately resulted in the development of cancer. We look forward to exploring how sequencing can provide the medical community with more specific, accurate data that can help guide cancer treatment options.”

As currently envisioned, patients enrolled in the study will have both tumor and normal tissue sequenced by TGen, Scripps, and other organizations, using Life Technologies’ Applied Biosystems SOLiD™ System to identify mutations. The SOLiD System is used globally in research experiments to better understand the genetic nature of diseases such as cancer, diabetes, and neurological disorders. Its throughput, accuracy and flexibility allow researchers to generate the high quality data needed for the advancement of molecular medicine.

The results will be validated by a CLIA-certified lab and interpreted by TGen and Omicia Inc, a personalized medicine company focused on interpreting genome sequences for clinical applications. A centralized tumor board for the study, composed of physicians from Fox Chase Cancer Center, TGen, Scripps and El Camino Hospital’s Genomic Medicine Institute, will study the results and consult with patients’ oncologists regarding how to use the test results to develop personalized care plans. Scripps Genomic Medicine, a program of the nationally renowned Scripps Health organization, is focused on using genetic information to create individual treatment plans. Fox Chase hosts the Institute for Personalized Medicine and, as a National Cancer Institute-designated Comprehensive Cancer Center, is one of the leading cancer treatment and research centers in the United States. The Genomic Medicine Institute at El Camino Hospital is nationally recognized for the support it provides to the medical community on clinical uses of genetic testing information.

Longer chemo better for early-stage node-positive breast cancer

Women with early-stage breast cancer—estrogen-negative or positive—with lymph node involvement benefit more from a 24-week regimen of chemotherapy than from 12 weeks of treatment. Interestingly, women who went into “chemopause”—chemotherapy-induced menopause—during treatment did better than women who did not. Read Web MD’s story on the research here. The research was published in the June 3 2010 New England Journal of Medicine.

Study Shows Race Not A Factor in ER-Negative Survival

African-American and white women from similar backgrounds treated similarly for estrogen-negative breast cancer had similar outcomes, according to research published in the May issue of the Journal of the American College of Surgeons. The bulk of the participants were from low-income neighborhoods in Louisiana and were treated at the Louisiana State University Health Services Center.

The five-year overall survival rates for both groups was 77 percent. Ten-year mortality rates were also similar, with 31 percent of the African-Americans dying in that time frame compared with 26 percent of the whites.

The study looked at 375 women with estrogen-negative disease who were treated from 1998 through 2008. Tumor size and grade; nodal involvement; and treatment were all similar. The whites had a slightly higher income than the African-American patients. African-Americans had a higher incidence of estrogen-negative (54 percent) than white women (39 percent.)

In previous studies, outcomes for African-Americans have been significantly worse than for whites. Some researchers argue that African-Americans might have a genetically different disease that responds poorly to typical treatments; others say the cause is socioeconomic. If the results of this study are borne out in future research, neither position may hold true. Race may be a factor in getting the disease, but not in overall reaction to treatment.

The study did not contain data on Her2, as it was not included in earlier data, so the results were not specific to triple-negative breast cancer.

TNBC Vaccine Expected—in 10 Years!

Based on the success of a recently concluded Stage II clinical trial, Vaxon Biotech plans to start Stage III trials of Vx-001, a vaccine that may be effective against triple-negative breast cancer. Stage III trials for breast cancer will begin in 2012-13 and Vaxon Biotech expects that a vaccine might be available for triple negative in 2020. Gee whiz! Hurry up, guys.

Read the somewhat thick news release here.

Clarification of Basal-like and Non-Basal Hormone-Negative Breast Cancer

ER-negative breast cancer has a poorer outcome than the ER positive disease in the short term, but in the long term, ER-negative disease subtypes actually have a better prognosis, according to a recent study in PLoS Medicine. Triple negative breast cancers can be divided into basal and non-basal, with the basal subtype having a poorer prognosis.

Survival patterns were independent of treatment, the researchers say, indicating that the biology of the tumor is the essential prognostic factor.

Three ER-negative subtypes exist, termed basal-like, HER2-positive, and normal breast-like tumors. Basal-like breast cancer is commonly identified by a lack of ER and HER2 receptor expression and by the expression of either cytokeratin 5/6 or epidermal growth factor receptor (EGFR). Many, but not all, triple-negative breast cancers are basal-like.

Read the entire study here.

Source:

Blows FM, Driver KE, Schmidt MK, Broeks A, van Leeuwen FE, et al. (2010) Subtyping of Breast Cancer by Immunohistochemistry to Investigate a Relationship between Subtype and Short and Long Term Survival: A Collaborative Analysis of Data for 10,159 Cases from 12 Studies. PLoS Med 7(5): e1000279.doi:10.1371/journal.pmed.1000279

Our Last View of the Cabin

Last fall, we left the cabin in the snow. It is beautiful, no matter what season.

It Takes a Family to Build a Cabin

Our cabin is near the East Spanish Peak in far southern Colorado. We’re about 150 miles south of Denver and about 10 miles off I-25. If you are driving from Denver to New Mexico, just south of Walsenburg, look to the right (west) and you will see a wonderful mountain. That is the East Spanish Peak. We are at the foot of that beauty. Make sure you wave at me. We enjoy great tranquility there, with our nearest neighbors being my brother and his wife, who are there six months a year. We are there four months. Our nearest full-time neighbor is two miles away. We built the cabin ourselves. Below is an essay I wrote while we were building.

It Takes A Family To Build A Cottage

In the shadow of a Colorado mountain sits a simple country cottage built by an electrical engineer, an Internet technician, a sculptor, a reporter, a filmmaker, and a college professor. It’s a 480-square-foot monument to the family and to the tricky relationship between self-reliance and interdependence.

The cottage and the family are mine. The electrical engineer is my brother Ed, who was the cabin’s building contractor, the man who knew what he was doing and taught the rest of us how to do it too. He and his son the Internet technician built the cabin’s shell—exterior walls, floors, windows, roof, electrical system and plumbing. The sculptor and reporter are my daughter and son; they installed the insulation, drywalled, built the deck, and finished the interior. The filmmaker is my sister-in-law Gwyn; she helped finish and paint the walls inside and out, using sand from the nearby creek to create a textured finish. I am the college professor; I did a little bit of just about everything, even though at the time I was sure all of it was way beyond my capabilities

Like many professionals, I typically hire experts to do work around the house—painters, plumbers, electricians—and enjoy the pragmatic reward of somebody else’s job well done. Build an entire mountain home myself? Why? How? Huh? My brother, however, simply assumed I could do it. Or, more important, we could do it. So we did. Now the best part of my mountain getaway is the fact that every nail in every board was driven by somebody I love.

In many ways, the decision to build it was a natural for us. Our dad built our family home, in addition to much of its furniture. I remember him showing me how to use a hammer as we worked together in his basement workshop: Hold the handle at the very end, and use a broad stroke to slam the nail in. I still occasionally hammer like a girl—holding the handle in the middle and tapping the nail delicately—but I am getting the hang of this construction business.

At the cottage, Ed took Dad’s role, showing us all how to hook this to that so that it wouldn’t leak, burn up, blow away, or crumble. We were all cooperative students, although he had to remind me regularly of the builder’s adage, “Measure twice, saw once.” I needed to measure about sixteen times and, even then, I had to use creativity to make boards fit because I was inevitably off. Finally, I got new glasses and learned to take my time. The result is one of those learning experiences we appreciate a great deal after the fact.

I now know how to use a power saw (I even have my very own). I know how to hide drywall seams (even though you can still see many of them at night when the lights are on). I know how to build a deck (it’s actually a trapezoid rather than the standard rectangle, but it does the trick). I know the pleasure of watching my scholarly children turn into handy workers who get a serious kick out of constructing a wall. And I know how it feels to fall asleep at night exhausted by physical activity, but thoroughly fulfilled by the work.

We’ve spent four summers building the cottage, and by now it is a comfy little haven, with water, solar power, and a composting toilet. Along the way, both of my sisters, two more nephews, a niece, and her nephew have come along to help dig holes, install the woodburning stove, paint, and do generally whatever is needed. It has truly been a labor of family love.

Our parents instilled in my siblings and me a strong appreciation of nature and a desire to spend as much time with it as possible. They also taught us how to treasure one another, so that the idea of living in a family enclave on the mountain had a special appeal. The land where the cottage perches is our inheritance from our parents, who asked us what we wanted with the money they had saved through decades of frugal living. It was an easy answer: mountain land. So now I own a little corner of alpine paradise with Ed and Gwyn, who have a home—which they also built themselves—down the road.

The cottage started as a cabin, because that is what I intended to build, but along the way, that word began to feel inadequate; it no longer seemed to do the homey little place justice. So we promoted it to cottage status. Another few rooms—maybe eighteen or so— and perhaps it will be an estate. Whatever the name, the cottage formerly known as a cabin is actually an outgrowth of my family in more than its construction, because mementos from my various homes create the warmth of the place. The kitchen sink, chairs, and curtains came from my parents’ house; the dining table is one my husband built me for our tenth anniversary; and the coffee table was crafted from the wooden camping cooler my dad made more than fifty years ago. The biggest memento, though, is the cottage itself.

When we are on the mountain, we share most of our dinners with whatever motley collection of family members happens to be there at the time, in a wonderful throwback to communal living. We eat well—grilled steaks, homegrown salads, and homemade cookies—and we eat it in a setting of immense beauty. The cottage faces a 13,000-foot mountain across a meadow of timothy grass. Bears, deer, and coyotes eye us through the woods across the meadow; eagles glide above.

As my family relaxes on our slightly cockeyed deck enjoying the mountain greenery, we also look at our handiwork and share a deep satisfaction in the fact that the charming building by which we sit would not have existed without our labor. We also share the realization that the outside needs more permanent siding than the original plywood it still sports; that there’s no place to store all our tools; that the deck needs a rail; and that we will never be truly finished.

But that’s fine. Being finished is overrated. As it turns out, the product we have been creating here is not only a mountain home. Our shared sweat, exhaustion, and exhilaration have built more than a simple cottage in the shadow of a mountain; it has been one step in a major work in progress—our family.

Summer Hours

We’re headed to our wee cabin in Colorado for the summer, where we enjoy gorgeous scenery, fresh air, lots of animals, and thoroughly lousy Internet. We are 8000 feet up and I am pretty sure our connection comes up the mountain on a goat. So, I will reduce my posts significantly. I’ll resume my regular updates in the fall.

Four Years Cancer-Free!

I have been felt up by two different doctors, had a mammogram and blood tests, plus an overall physical. No signs of cancer. Yea!!!!!!!!!! The mammo technician, though, gave me a scare, saying I have calcifications on the breast that had the cancer and doctors have been watching them because they can be a sign of early cancer. "Oh, great," I thought. I asked my surgeon who explained that I do, in fact, have calcifications in my affected breast, caused by the trauma it has gone through. "Most of the women I see have calcifications," he said. Mine are dispersed and stable--they have not changed in four years. Most important, they are not clustered. Clustered calcifications can be a sign of early cancer. According to my surgeon, though, they lead to cancer about five percent of the time, which means even if mine were micros, I still had a 95 percent chance they were not cancerous. Why did the tech mention that and why did she mention it the way she did? I swear, people need to think before they speak far more often than they do.

So I learned something new. I guess I have been oblivious to this, or else nobody thought to mention it to me. Whatever the case, four years cancer-free! Time to celebrate.

Markers Linked to Estrogen-Negative Breast Cancer

From a news release from the National Institutes of Health:

Scientists have identified a group of surface markers on cells linked to an aggressive type of breast cancer called estrogen receptor-negative cancer. In this preliminary study, estrogen-negative breast cancer developed when three markers, CD44+, CD49fhi, and CD133hi were present simultaneously on the surface of human cells taken from breast cancer patients and transplanted into a mouse; this is called a xenograft model. The scientists named these human cells with tumor-forming ability in mice, xenograft-initiating cells, or XIC. The research, conducted by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health, appeared online May 18, 2010, and in print June 1, 2010, in Cancer Research.

Surface markers, usually proteins, are visualized on many cell types using antibodies or other detection methods. To identify surface markers of estrogen receptor-negative breast cancer stem-like cells, the investigators tested different populations of human breast cancer cells for their ability to form tumors when injected into the fat pads of the mammary glands of mice with compromised immune systems. The various tumor cell populations were prepared by a technique called flow cytometry, in which distinct antibodies bind to specific cell surface markers, resulting in separate subpopulations of cells.

The identification of specific markers on cells that are associated with estrogen receptor-negative breast cancer is important because this type of breast cancer is more difficult to treat than estrogen receptor-positive breast cancer. Estrogen receptor-positive breast cancers may be treated with medications such as tamoxifen, which interfere with the activity of estrogen. But no targeted therapies are yet available for patients with estrogen receptor-negative breast tumors. These cancers are currently treated with chemotherapy drugs that are toxic to many cells, not just cancer cells, and which can be hard for patients to tolerate.

"We are excited but cautious at the prospect that the presence of the XIC markers on estrogen receptor-negative breast cancer cells may present a selective target for early detection imaging and for personalized therapy," said Barbara K. Vonderhaar, Ph.D., NCI scientist emeritus of the Mammary Biology and Tumorigenesis Laboratory, Center for Cancer Research. Read more.

My Belated Breast Cancer Anger

My acupuncturist told me today that I am tense. “What have you got to be tense about?” she teased. I immediately blamed the two articles I have due in the next week, plus the book I am writing.

But that did not ring true. I have spent my life fighting deadlines. Why would they start bothering me now?

Then, she said, “I think beneath this all there is some anger.”

Bingo.

Four years after my diagnosis, I am finally starting to get royally ticked off that I had cancer. One catalyst for this anger is that I came across the statistics from the National Cancer Institute estimating that 12.7 percent of all women will face breast cancer in their lives. So that means that 87.3 percent of all women will NOT face breast cancer.

After being positive and upbeat and shrugging this thing off for years, I am now starting to ask, “Why me?”

But why now?

I think I used all my positive energy to fight this thing and am only now feeling safe enough to get cranky about being selected for this elite club.

I am also facing my various doctors’ visits and mammograms and blood tests and all the whooha that we all deal with three or four times a year. I am tired of it. Tired of these regular worries about what might come. Are they going to find something this year? Has it come back after all this time?

Remaining positive is wearing on me. My husband says there’s no reason to think they will find anything this time—I am feeling fine and have no symptoms, yada, yada, yada. But, I tell him, if there is no risk, why do they do the tests at all?

And then that ticks me off. I remember so many friends who passed their tests and then ended up with a cough, a bump, a whatever, and the nasty stuff was back.

Yet, others catch something early and take care of it. I have talked with women who are years past a recurrence of triple negative, so a recurrence is not a death sentence.

Because my original diagnosis was not as frightening as most—a small tumor and no positive nodes—I sometimes have felt that I am not as justified in complaining as others. A friend recently told me that somebody had called hers a “fake cancer” because it was hormone positive and less than a centimeter. But, even though she has a better prognosis, she still faces the possibility of cancer returning. We all do. It happened once and we are forever on our guard.

That stinks.

Plus, I wonder, if this did come back, what would I do? Go through chemo again? I am truly not sure. I might just take my savings and hop a plane to travel the world.

In a few days I hope to post an update on being four years cancer-free. Still, I would rather not be dealing with all this at all.

I am pretty sure I am not alone in that feeling.

Asian Women Have Higher Rate or ER/PR-Negative

Women under 40 with Asian Indian/Pakistani roots have a higher rate of estrogen-negative and progesterone-negative breast cancer--both invasive ductal and inflammatory—than Caucasians. Researchers used data from the United States National Cancer Institute's Surveillance Epidemiology and End Results (SEER) Cancer program to study 360,933 breast cancer cases diagnosed from 1988 to 2006.

Some stats on Asian Indian/Pakistani breast cancer patients:

• 16.2 percent were under 40 years old compared to 6.23 percents of Caucasians.

• They had more invasive ductal carcinoma and inflammatory cancer, and less invasive lobular carcinoma than Caucasians.

• Adjusting for stage at diagnosis, age, tumor grade, nodal status, and histology, Asian Indian/Pakistani women's survival was similar to Caucasians, while African Americans' was worse.

Read the abstract or get a PDF of the article here.

SOURCE: Kakarala, Madhuri, Rozek, Laura, Cote, Michele, Liyanage, Samadhi Brenner, Dean, 'Breast cancer histology and receptor status characterization in Asian Indian and Pakistani women in the U.S. - a SEER analysis', BMC Cancer , vol. 10, no. 1, 191+ (2010).

Latino Link to TNBC to Be Studied

The Fred Hutchinson Cancer Research Center has been awarded $10.24 million from the National Institutes of Health to lead a five-year look at breast cancer among Hispanic women. Among issues to be studied are the links to TNBC and overexpressing HER2 cancers in this group. Ten institutions across the country will contribute to the research. Read more on Medical News Today.