Progress on BIG 1-02/IBCSG 27-02/NSABP B-37, a prospective randomized trial evaluating chemotherapy after local therapy for isolated locoregional recurrences of breast cancer

BACKGROUND: The utility of chemotherapy for women who experience a locoregional recurrence after primary treatment of early breast cancer remains an open question. An international collaborative trial is being conducted by the Breast International Group (BIG), the International Breast Cancer Study Group (IBCSG), and the National Surgical Adjuvant Breast and Bowel Project (NSABP) to determine the effectiveness of cytotoxic therapy for these patients, either alone or in addition to selective use of hormonal therapy and trastuzumab. METHODS: The trial population includes women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery, but subsequently develop an isolated local and/or regional ipsilateral invasive recurrence. Excision of all macroscopic tumor without evidence of systemic disease is required for study entry. Patients are randomized to receive chemotherapy or no chemotherapy; type of chemotherapy is not protocol-specified. Radiation, hormonal therapy, and trastuzumab are given as appropriate. The primary endpoint is disease-free survival (DFS). Quality-of-life measurements are collected at baseline, and then at 9 and 12 months. The accrual goal is 977 patients. RESULTS: This report describes the characteristics of the first 99 patients. Sites of recurrence at study entry were: breast (56%), mastectomy scar/chest wall (35%), and regional lymph nodes (9%). Two-thirds of patients have estrogen-receptor-positive recurrences. CONCLUSION: This is the only trial actively investigating the question of "adjuvant" chemotherapy in locally recurrent breast cancer. The case mix of accrual to date indicates a broad representation of this patient population.

A randomized clinical trial of adjuvant chemotherapy for radically resected locoregional relapse of breast cancer: IBCSG 27-02, BIG 1-02, and NSABP B-37

In this phase III, multinational, randomized trial, the International Breast Cancer Study Group, Breast International Group, and the National Surgical Adjuvant Breast and Bowel Project will attempt to define the effectiveness of cytotoxic therapy for patients with locoregional recurrence of breast cancer. We will evaluate whether chemotherapy prolongs disease-free survival and, secondarily, whether its use improves overall survival and systemic disease-free survival. Quality of life measurements will be monitored during the first 12 months of the study. Women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery and who have undergone complete surgical excision of all macroscopic disease but who subsequently develop isolated local and/or regional ipsilateral invasive recurrence are eligible. Patients are randomized to observation/no adjuvant chemotherapy or to adjuvant chemotherapy; all suitable patients receive radiation, hormonal, and trastuzumab therapy. Radiation therapy is recommended for patients who have not received previous adjuvant radiation therapy but is required for those with microscopically positive margins. The radiation field must encompass the tumor bed plus a surrounding margin to a dose of >or= 40 Gy. Radiation therapy will be administered before, during, or after chemotherapy. All women with estrogen receptor-positive and/or progesterone receptor-positive recurrence must receive hormonal therapy, with the agent and duration to be determined by the patient's investigator. Adjuvant trastuzumab therapy is permitted for those with HER2- positive tumors, provided that intent to treat is declared before randomization. Although multidrug regimens are preferred, the agents, doses, and use of supportive therapy are at the discretion of the investigator.

Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: the BIG 1-98 trial

PURPOSE: To explore potential differences in efficacy, treatment completion, and adverse events (AEs) in elderly women receiving adjuvant tamoxifen or letrozole for five years in the Breast International Group (BIG) 1-98 trial. METHODS: This report includes the 4,922 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial. The median follow-up was 40.4 months. Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was used to examine the patterns of differences in disease-free survival and incidences of AEs according to age. In addition, three categoric age groups were defined: "younger postmenopausal" patients were younger than 65 years (n = 3,127), "older" patients were 65 to 74 years old (n = 1,500), and "elderly" patients were 75 years of age or older (n = 295). RESULTS: Efficacy results for subpopulations defined by age were similar to the overall trial results: Letrozole significantly improved disease-free survival (DFS), the primary end point, compared with tamoxifen. Elderly patients were less likely to complete trial treatment, but at rates that were similar in the two treatment groups. The incidence of bone fractures, observed more often in the letrozole group, did not differ by age. In elderly patients, letrozole had a significantly higher incidence of any grade 3 to 5 protocol-specified non-fracture AE compared with tamoxifen (P = .002), but differences were not significant for thromboembolic or cardiac AEs. CONCLUSION: Adjuvant treatment with letrozole had superior efficacy (DFS) compared with tamoxifen in all age groups. On the basis of a small number of patients older than 75 years (6%), age per se should not unduly affect the choice of adjuvant endocrine therapy.

Biomechanics of meniscal horn attachments

Menisci are anchored to the tibia by means of ligament-like structures called meniscal attachments. Failure material properties of bovine meniscal attachments were obtained. There were no significant differences in the structural properties or ultimate stress between the meniscal attachments (p>0.05). Furthermore, Glycosaminoglycan (GAG) fraction and crimping frequency was obtained for each attachment using histology and differential interference contrast (DIC) respectively. Results showed that the anterior attachment’s insertion had the greatest GAG fraction when compared to the posterior attachment’s insertion. Crimp frequency of the collagen fibrils was homogeneous along the length. Moreover, Scanning Electron Microscopy (SEM) technique was used to reveal the morphology of collagen in human meniscal attachments. Its midsubstance was composed of collagen fascicles running parallel to the longitudinal axis, with a few fibrils running obliquely, and others transversely. There were no differences between attachments for crimping angle or length. Since ligamentous-type tissues are comprised mainly of water, the fluid pressure within meniscal horn attachments was measured using a Fiber Optic Microsensor (FOM). Four cadaveric human joints were subjected to 2BW compressive load (ramp) at 0-, 15-, and 30-degrees of flexion for a minute and then the load was hold for 20 minutes (equilibrium). There were significant differences between 0- and 15- (p1– c5) were obtained. Significant differences were found on the straightened collagen fibers coefficient (c5) between MP and LA attachments (p

A Microscopic Study of some Volcanic Rocks in the Vicinity of Butte

The rhyolite rocks in the vicinity of Big Butte present a very interesting, though complicated study. It seems that no extensive or conclusive work has ever been done upon these extrusives. I have found that the rhyolites present a very interesting problem, especially microscopically, and that no doubt an intensive study along these lines will solve the problems concerning age relations of different flows and origin of the magma that produced the material for emanations.

A Preliminary Study of the Ostracoda of the Big Snowy Group, Mississippian, of Montana.

In the field, samples were taken vertically and horizon­tally along the various outcrops in different sections of central and south-central Montana. At important localities the samples were taken about every half-foot verti­cally; in other sections they were taken every few feet.

Archeological Investigations at the Big Creek Lake Site (24RA34)

In August 1977 excavation was conducted at the Big Creek Lake site -24RA34- at the outlet of the 91g Creek Lakes, Selway-Bitterroot Wilderness Area, Ravalli County, Montana. The site contained shallow, disturbed deposits and lacks any statisgraphic separation. One of these occupations was identified by a projectile point type not previously reported from the area. This was termed Big Creek Corner Notched and its temporal affiliation is not precisely known. Comparative material from Colorado and Alberta suggest either Early Archaic or Late Archaic affiliation. The occupations exemplified by Big Creek Corner Notched points and by Pelican Lake-Elko points (Late Archaic 1000 B.B – A.D. 200) were the most prevalent at the site. Less intensive occupations are by ·Middle Plains Archaic McKean points and Late Prehistoric small side notche arrow points. Microscopic analysis of tool working edges shows several of the projectile point forms were used as multi-functional implements. especially as butchering tools. Many of the types of chipped stone recovered from the site are from known sources in western Montana; indicating group movements within the eastern portion of the Intermountain region. Based on the numerous projectile points and cutting tools, the site is interpreted as a seasonally occupied base camp for hunters.

An Investigation of the Ores of the Big Seven Mine, Neihart, Montana

During the course of this investigation of the ores of the Big Seven mine, Neihart, Montana, the writer has attempted, through a mi­croscopic study of polished sections, to ascertain the hypogene or supergene character of the ore minerals present in the ore suite.

Subsurface to Surface Correlation of the Tensleep Sandstone in the West Flank of the Pryor Mountains in Carbon County, Montana

The Pennsylvanian Tensleep Sandstone is an eolian and nearshore marine/sabka quartz arenite unit with prominent outcrops along the western Pryor/Bighorn Mountain front east of Red Lodge, MT. Regionally, the formation represents one of the largest ergs in the global geologic record. High permeability makes it an important oil and gas reservoir and aquifer in south central Montana and throughout much of Wyoming. The Tensleep Sandstone’s high percentage of quartz content and grain roundness, due to its eolian origin, makes it a prospective source for natural proppant sand. Three continuous 4-inch cores were obtained during a cooperative project between Montana Tech and industry partners. Using stratigraphic sections, cores, thin sections, and x-ray fluorescence (XRF) analysis, the usefulness and economic feasibility of the Tensleep Sandstone as a minable hydraulic fracture proppant was explored. Usefulness depends on cementation, grain shape, grain size, and depth from surface of the prospective zone. Grain shape and size were determined by thin sections, sieving, and stereomicroscope analysis. Analysis of 20 disaggregated sand samples has shown that as much as 30 percent of the grain sizes fall between 30-50 mesh (medium- to finegrained sand size) and about 45 percent of the grain sizes fall between 70–140 mesh (very fine-grained sand to coarse silt), grain sizes appropriate for some hydraulic fracture operations. Core descriptions and XRF data display the distribution of lithology and cementation. Core descriptions and XRF data display the distribution of lithology and cementation. Elemental (XRF) analyses help to delineate more pure quartz sands from those with grain fractions reflecting fine-grained clastic and evaporitic inputs. The core and nearby stratigraphic sections are used to quantify the amount of overburden and the 3 amount of resource in the area. Initial results show favorable crush strength and useable grain size and shape.

Legislative Legacy: Big Changes in Legislative Article of 1972 Constitution -- Jerry Loendorf, Arlyne Reichert & Rich Bechtel “In the Crucible of Change”

The fulcrum upon which were leveraged many of the dramatic progressive changes in Montana that are documented "In the Crucible of Change" series was the lead up to, preparation, writing and adoption of the 1972 Montana Constitution. As Montana citizens exhibited their concern over the dysfunctional state government in MT under its 1889 Constitution, one of the areas that stood out as needing serious change was the Montana Legislature. Meeting for only sixty calendar days every two years, the Legislature regularly tried to carry off the subterfuge of stopping the wall clock at 11:59 PM on the sixtieth day and placing a shroud over it so they could continue to conduct business as if it were still the 60th day. Lawyers hired by the Anaconda Company drafted most bills that legislators wanted to have introduced. Malapportionment, especially in the State Senate where each county had one Senator regardless of their population, created a situation where Petroleum County with 800 residents had one senator while neighboring Yellowstone County with 80,000 people also had one senator -- a 100-1 differential in representation. Reapportionment imposed by rulings of the US Supreme Court in the mid-1960s created great furor in rural Montana to go along with the previous dissatisfaction of the urban centers. Stories of Anaconda Company “thumbs up – thumbs down” control of the votes were prevalent. Committee meeting and votes were done behind closed doors and recorded votes were non-existent except for the nearly meaningless final tally. People were in the dark about the creation of laws that affected their daily lives. It was clear that change in the Legislature had to take the form of change in the Constitution and, because it was not likely that the Legislature would advance Constitutional amendments on the subject, a convention seemed the only remedy. Once that Convention was called and went to work, it became apparent that the Legislative Article provided both opportunity for change and danger that too dramatic a change might sink the whole new document. The activities of the Legislative Committee and the whole Convention when acting upon Legislative issues provides one of the more compelling stories of change. The story of the Legislative Article of the Montana Constitution is discussed in this episode by three major players who were directly involved in the effort: Jerry Loendorf, Arlyne Reichert and Rich Bechtel. Their recollections of the activities surrounding the entire Constitutional Convention and specifically the Legislative Article provide an insider’s perspective of the development of the entire Constitution and the Legislative portion which was of such a high degree of interest to the people of Montana during the important period of progressive change documented “In the Crucible of Change.” Jerry Loendorf, who served as Chair of the Legislative Committee at the 1972 Montana Constitutional Convention, received a BA from Carroll College in 1961 and a JD from the University of Montana Law School in 1964. Upon graduation he served two years as a law clerk for the Montana Supreme Court after which he was for 34 years a partner in the law firm of Harrison, Loendorf & Posten, Duncan. In addition to being a delegate to the Constitutional Convention, Jerry served on the Board of Labor Appeals from 2000 to 2004. He was designated a Montana Special Assistant Attorney General to represent the state in federal court on the challenge to the results of the ratification election of Montana's Constitution in 1972. Jerry served on the Carroll College Board of Directors in the late 1960s and then again as a member of the Board of Trustees of Carroll College from 2001 to 2009. He has served on the Board of Directors of the Rocky Mountain Development Council since 1970 and was on the board of the Helena YMCA from 1981 to 1987. He also served on the board of the Good Samaritan Ministries from 2009 to 2014. On the business side, Jerry was on the Board of Directors of Valley Bank to Helena from 1980 to 2005. He is a member of the American Bar Association, State Bar of Montana, the First Judicial District Bar Association, and the Montana Trial Lawyers Association. Carroll College awarded Jerry the Warren Nelson Award 1994 and the Insignias Award in 2007. At Carroll College, Jerry has funded the following three scholarship endowments: George C and Helen T Loendorf, Gary Turcott, and Fr. William Greytek. Arlyne Reichert, Great Falls Delegate to the Constitutional Convention and former State Legislator, was born in Buffalo, NY in 1926 and attended University of Buffalo in conjunction with Cadet Nurses Training during WWII. She married a Montanan in Great Falls in 1945 and was widowed in 1968. She is mother of five, grandmother of seven, great-grandmother of four. Arlyne was employed by McLaughlin Research Institute in Great Falls for 23 years, serving as Technical Editor of Transplantation Journal in 1967, retiring as Assistant Director in 1989. In addition to being a state legislator (1979 Session) and a delegate to the 1972 Montana Constitutional Convention, she has filled many public roles, including Cascade County Study Commissioner (1974), MT Comprehensive Health Council, US Civil Rights Commission MT Advisory Committee, MT Capitol Restoration Committee, and Great Falls Public Library Trustee. Arlyne has engaged in many non-profit activities including League of Women Voters (State & Local Board Officer – from where her interest in the MT Constitutional change developed), Great Falls Public Radio Association (President & Founder), American Cancer Society (President Great Falls Chapter), Chair of MT Rhodes Scholarship Committee, and Council Member of the National Civic League. She also served a while as a Television Legislative Reporter. Arlyne has been recipient of numerous awards, the National Distinguished Citizens Award from the National Municipal League, two Women of Achievement Awards from Business & Professional Women, the Salute to Women Award by YWCA, Heritage Preservation Award from Cascade County Historical Society and the State of Montana, and the Heroes Award from Humanities Montana. She remains active, serving as Secretary-Treasurer of Preservation Cascade, Inc., and as Board Member of the McLaughlin Research Institute. Her current passion is applied to the preservation/saving of the historic 10th Street Bridge that crosses the Missouri River in Great Falls. Rich Bechtel of Helena was born in Napa, California in 1945 and grew up as an Air Force brat living in such places as Bitberg, Germany, Tripoli, Libya, and Sevilla, Spain. He graduated from Glasgow High School and the University of Montana. Rich was a graduate assistant for noted Montana History professor Professor K. Ross Toole, but dropped out of graduate school to pursue a real life in Montana politics and government. Rich has had a long, varied and colorful career in the public arena. He currently is the Director of the Office of Taxpayer Assistance & Public Outreach for MT’s Department of Revenue. He previously held two positions with the National Wildlife Federation in Washington, DC (Sr. Legislative Representative [1989-91] and Sr. Legislative Representative for Wildlife Policy [2004-2006]). While in Washington DC, he also was Assistant for Senator Lee Metcalf (D-MT), 1974-1976; Federal-State Coordinator for State of Montana, 1976-1989; Director of the Western Governors’ Association Washington Office, 1991-2000; and Director of Federal Affairs for Governor Kitzhaber of Oregon, 2001- 2003. Earlier in Montana Government, between 1971 and 1974, Rich was Research Analyst for MT Blue Ribbon Commission on Postsecondary Education, Legislative Consultant and Bill Drafter for MT Legislative Council, Research Analyst for the MT Constitutional Convention Commission where he provided original research on legislatures, as well as Researcher/Staff for the MT Constitutional Convention Legislative Committee, from where he drafted the various provisions of the Legislative Article and the majority and minority reports on behalf of the Committee members. Rich has represented Montana’s Governor on a trade and cultural mission to Republic of China and participated in US-German Acid Rain Committee sessions in Germany and with European Economic Community environmental officials in Belgium. He is married to Yvonne Seng (Ph.D.) - T’ai Chi apprentice; author and birder.

A Geological Report on Several Localities in the Northwestern Tobacco Root Mountains

To better acquaint seniors in Geology and mining with actual field practice, the Montana School of Mines offer a course in Geologic Field Mapping, during the three weeks preceding the opening of the fall semester. The first two weeks are spent in actual field mapping of the geologic formations near Whitehall, Montana, while the third week is spent back on the campus compiling data and finishing maps started in the field.

Big Change Coming: Gov. Forrest Anderson’s Unprecedented Preparation for Bringing Change to Montana – Newell Anderson & Brian Shovers “In the Crucible of Change”

Abstract to be posted.

Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial

BACKGROUND: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. METHODS: We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment. RESULTS: The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy. CONCLUSIONS: Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients.