Trans-ethnic predicted expression genome-wide association analysis identifies a gene for estrogen receptor-negative breast cancer

Trans-ethnic predicted expression genome-wide association analysis identifies a gene for estrogen receptor-negative breast cancer

There are some amazing things happening right now on the battle against breast cancer! Stay Tuned!

Androgen receptor expression on circulating tumor cells in metastatic breast cancer

Androgen receptor positive breast cancer

I have heard of cases where androgen receptors were present on breast cancer cells, but had no idea it was so common. I wonder how this will affect treatment paradigms over time?

Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer

HER2-positive breast cancer

It appears pertuzumab, when used along side Trastuzumab and chemotherapy, improves the rates of invasive-disease-free survival among patients with early stage, HER2-positive breast cancer.

 

Sunday Run Day Fun Day

This was a very fun, yet challenging run! I worked out (biceps/triceps/ Zumba) and ran the day (3.5 mi) before as I completely forgot about this run. I normally would take at least one day off before a race. Also, I have been on a low carb diet (~25 grams/day of carbohydrates). My legs begin to burn within the first 5 minutes into the race. I typically do not experience this until I am nearly 3 miles into a run of similar pace, so this short race became as much mental as it was physical. I thank the Lord that I was able to finish this run.

After which, I went to church and had a wonderful time as usual!

Savage 7k Run Results

 

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Breast Cancer Research and Treatment

Strut-adjusted volume implant (SAVI) brachytherapy-based accelerated partial breast irradiation (APBI) in African American women

Abstract

Purpose

To examine the clinical outcomes of postmenopausal African American (AA) women treated with strut-adjusted volume implant brachytherapy-based accelerated partial breast irradiation for early-stage node-negative breast cancer.

Methods

From January 2011 through April 2015, a total of 50 AA patients, meeting criteria to receive APBI as defined by the National Surgical Adjuvant Breast and Bowel Project B-39 (NASBP B-39), completed treatment with the SAVI breast brachytherapy device at Howard University Hospital.

Results

4% ipsilateral breast tumor recurrence and 2% breast cancer-specific mortality was observed. Median follow-up has been 3.8 years with a range of 0.29–4.69 years. Dosimetry parameters yielded a median V90 of 96.22% (range 77.86–105.00%), a median V150 of 31.27 cm³ (range 23.30–49.15 mL), and a median V200 of 14.53 cm³ (range 5.92–19.38 mL). Cosmesis was excellent. There were no infections, persistent seromas, fat necrosis, or telangiectasias observed to date.

Conclusions

This study is the first study to describe the use of SAVI as APBI in an exclusively AA population. This study has demonstrated excellent local control in appropriately selected patients, similar clinical outcomes to the general population, and good to excellent cosmesis in AA women to date.

Biochemistry and Anesthesiology

Either of these two links:

https://mayoclinic.pure.elsevier.com/en/publications/naadp-as-a-second-messenger-neither-cd38-nor-base-exchange-reaction

American Journal of Physiology Cell

NAADP as a second messenger: Neither CD38 nor base-exchange reaction are necessary for in vivo generation of NAADP in myometrial cells

Sandra Soares, Michael Thompson, Thomas White, Amir Isbell, Michiko Yamasaki, Yodeta Prakash, Frances E. Lund, Antony Galione, Eduardo N. Chini

Abstract

Nicotinic acid adenine dinucleotide phosphate (NAADP) has recently been shown to act as a second messenger controlling intracellular Ca²⁺ responses in mammalian cells. Many questions remain regarding this signaling pathway, including the role of the ryanodine receptor (RyR) in NAADP-induced Ca²⁺ transients. Furthermore, the exact metabolic pathway responsible for the synthesis of NAADP in vivo has not been determined. Here, we demonstrate that the NAADP mediated Ca²⁺ release system is present in human myometrial cells. We also demonstrate that human myometrial cells use the NAADP second messenger system to generate intracellular Ca²⁺ transients in response to histamine. It has been proposed in the past that the NAADP system in mammalian cells is dependent on the presence of functional RyRs. Here, we observed that the histamine-induced Ca²⁺ transients are dependent on both the NAADP and inositol 1,4,5-trisphosphate signaling pathways but are independent of RyRs. The enzyme CD38 has been shown to catalyze the synthesis of NAADP in vitro by the base-exchange reaction. Furthermore, it has been proposed that this enzyme is responsible for the intracellular generation of NAADP in vivo. Using CD38 knockout mice, we observed that both the basal and histamine stimulated levels of NAADP are independent of CD38 and the base-exchange reaction. Our group is the first to demonstrate that NAADP is a second messenger for histamine-elicited Ca²⁺ transients in human myometrial cells. Furthermore, the NAADP mediated mechanism in mammalian cells can be independent of RyRs and CD38. Our data provides novel insights into the understanding of the mechanism of action and metabolism of this new second messenger system. Copyright © 2007 the American Physiological Society.

HPV + SCC of Unknown Primary

Any of these 3 links:

GynOncReports

gyn pub med

Elsevier

Three cases of women with HPV-related squamous cell carcinoma of unknown primary in the pelvis and retroperitoneum: A case series.

Isbell A¹, Fields EC².

Author information

 

Abstract

BACKGROUND:

Carcinoma of unknown primary (CUP) of the pelvis is a challenging entity for the oncologist. The role of human papilloma virus (HPV)/p16 in carcinogenesis and prognosis is more established in the head and neck than in the pelvis. In the case of an HPV positive occult primary of the pelvis the radiation therapy target coverage is not well established.

CASE REPORTS:

Case#1: A 69-year-old female with a left retroperitoneal and pelvic mass was treated with chemoradiation to a dose of 45 Gy in 25 fractions to elective lymph node regions and simultaneous boost to FDG-avid lymph nodes to 55 Gy in 25 fractions. A post-treatment PET-CT showed complete response of disease now 7 months post treatment. Case#2: A 58-year-old female with a large left retroperitoneal pelvic mass was treated post-operatively with chemoradiation to 45 Gy in 25 fractions with a pelvic boost to 54 Gy. She is clinically and radiographically with no evidence of disease at 4 years. Case#3: A 47-year-old female with left sided retroperitoneal pelvic mass that declined therapy. She ultimately died of progressive disease at 1 year after diagnosis.

CONCLUSION:

Cisplatin based chemoradiation is effective for treating HPV/p16 + pelvic squamous cell cancers of unknown primary as long as the mass, regional lymph nodes and high risk pelvic primary sites are adequately covered.

KEYWORDS:

Carcinoma of unknown primary; Chemoradiation; HPV positive; Pelvis and retroperitoneum; Squamous cell carcinoma; p16 positive

Rare Paravertebral and Skull Base Metastases in Prostate Cancer

Any of these three:

Prostate and Skull pubpdf website

Karger prostate and skull

prostate and skull pubmed

 

Abstract

Prostate cancer is the most commonly diagnosed visceral cancer in the United States. A majority of cases exhibit an insidious course and nonaggressive tumor behavior. Prostate cancer can manifest as lesions which remain localized, regionally invading or metastasize to lymph nodes, bones, and lungs. Here, we report a unique case of metastatic prostate cancer to the right upper mediastinum, presenting as a paravertebral mass within 2 years of initial tissue diagnosis. Paravertebral spread has not been described for prostate cancer, and herein, we discuss the clinical presentation, diagnostic workup, and possible therapeutic options available in light of the literature.

Introduction

Prostate cancer is the most commonly diagnosed visceral cancer [1], and the second leading cancer and cause of cancer deaths in men in the United States [2]. Autopsy series have detected prostate cancer in about 1 out of 3 of men aged 55 years and in about 3 out of 5 men by age 80 years [3]. Disease survival is prognosticated by many factors, and in particular by tumor extent at the time of diagnosis. Five-year relative survival in men with localized disease is 100%, compared to <30% among those with metastases. The most common sites of metastasis are the bone, lung, and liver [4]. Paravertebral metastasis from prostate cancer is rare, with only a limited number of cases reported. We discuss an interesting case of prostate cancer with paravertebral metastasis and present an approach to management.

Case Presentation

The patient was a 55-year-old African-American man with a history of prostate cancer (diagnosed via core needle biopsy 2 years prior). At that time, the patient had 6 specimens obtained from different prostatic tissue locations submitted for histopathology. Four out of the 6 specimens showed benign prostate tissue in the left apex, right apex, left mid, and left base. The remaining 2 specimens showed prostatic adenocarcinoma in the right base and right mid zones, respectively: a Gleason score of 9 (5+4) was noted in 4 out of 4 submitted core segments from the right base, and a Gleason score of 8 (4+4) in 3 out of 3 core segments from the right mid zone. No therapy (chemotherapy, hormonal, or radiation) was implemented prior to presentation to our facility. He reported previously treated Lyme disease and chronic kidney disease stage 3, and complained of right neck pain that had started after a mechanical fall. He denied any trauma to the head, loss of consciousness, syncopal symptoms, any weakness in his lower extremities, unsteady gait or numbness, or tingling in his extremities. The patient also reported recent onset of coughing spells associated with drinking of fluids.

MRI of the thoracic spine disclosed significant compression of the T4 vertebral body with mild associated cord compression, and diffuse patchy enhancement throughout the thoracic spine. Initial CT scans revealed no acute bony trauma, but showed multiple destructive lytic lesions and partial sclerosis in the lower calvarium (Fig 1), both clavicles, and the lower cervical and thoracic vertebra (Fig 2). A paravertebral mass in the right upper mediastinum was also visualized (Fig 3). Subsequent MRI images of the brain with and without contrast displayed a right-sided, 1.3 × 4.3 × 2.5 cm, intermediate-signal mass at the base of the skull in both the T1- and T2-weighted sequences. Chest X-rays revealed a small right lung apical opacity with probable destruction of adjacent first and second ribs. Further workup showed small sclerotic densities in the left sacrum and right iliac bone, assessed as metastasis. Multiple myeloma workup, including serum and urine protein electrophoresis, immunofixation, beta-2 microglobulin, and serum free light chain quantification, was negative. The serum PSA level was elevated at 994.47 ng/ml.

To further assess the extent of disease, a bone scan was obtained after administering 26 mCi of technetium-99m methylene diphosphonate intravenously. This revealed multiple foci of abnormally increased tracer accumulation involving multiple ribs bilaterally as well as the cervical, thoracic, and lumbar spine (Fig 4). Small foci of increased tracer accumulation were also noted in the humeral shafts, left proximal femur, and left mid femoral shaft. MRI of the cervical and thoracic spine with and without contrast revealed diffuse, patchy, bony metastases and a paraspinal mass on the right, extending from T1 to T4 and measuring approximately 7 cm in craniocaudal dimension, with significant compression of the T4 vertebral body with mild associated cord compression (Fig 5). MRI of the brain also revealed a contrast-enhancing mass at the base of the skull on both the T1 and FLAIR sequences (Fig 6).

The patient’s symptoms (choking spells and neck pain) were attributed to cord compression as evident on MRI imaging, and he was started on dexamethasone for symptom relief. He was also started on 6 cycles of chemotherapy with Taxotere in addition to intramuscular leuprolide for treatment of his prostate cancer, given the extensive burden of his disease. Radiation oncology was consulted for consideration of radiotherapy to the lesion at the base of his skull and the paravertebral mass. They formulated a treatment plan of 2.5 Gy per fraction doses of external beam radiation to the skull base in 14 fractions for a total dose of 35 Gy, and 2.5 Gy per fraction doses of radiation to the paravertebral mass in 14 fractions for a total dose of 35 Gy. The patient’s coughing paroxysms associated with swallowing resolved after just 2 sessions of radiotherapy.

The patient has had 4 cycles of chemotherapy thus far and is responding well to treatment. Restaging/surveillance imaging will be obtained once he has completed 6 cycles of chemotherapy.

Discussion

Prostate cancer is the second leading cause of cancer in men in the United States [2], and an important cause of cancer-related deaths in this demographic group. In particular, African-American men were found to have an incidence of 203.5 cases per 100,000 between 2009 and 2013 [5]. This is higher than the incidence in Caucasians (121.9), Hispanics (106.9), and Asians/Pacific Islanders (68.9) [5]. Blacks were also found to be more than twice as likely to die of prostate cancer as men belonging to other races [5].

This disparity in outcome is likely multivariate, and while the role of demographics and race remains to be better understood, investigating tumor cytogenetics offers a promising method to predict disease aggressiveness and outcomes. Genome-wide association studies and meta-analyses have shed light onto susceptibility loci for prostate cancer, including single nucleotide polymorphisms that may portend disease aggressiveness [6–10]. The advent of genome-wide association studies has identified 78 susceptibility loci (single nucleotide polymorphisms) associated with risk of prostate cancer [10]. While further studies are required to make them viable tools for risk stratification in clinically useful ways, these gene loci offer specific regions of interest for new research to focus on.

A puzzling piece in this clinical case was the actual route of metastasis to the mediastinum. In this regard, prior autopsy studies spanning over 19,000 cases in men, carried out between 1967 and 1995, identified 1,589 cases of prostate cancer and considered likely routes of metastasis [4]. Roughly one-third of prostate cancer cases were found to have hematogenous spread. Of these, 90% metastasized to the bone, 46% to the lung, 25% to the liver, 21% to the pleura, and 13% to the adrenals. This study reiterated the classical hematogenous spread via the vena cava, but also identified upward metastatic spread along the spinal veins after metastasization to the lumbar spine, which was hypothesized to occur early in the metastatic process [4]. The venous vertebral plexus was described fully in 1940 [11] and extends from the sacrum to the cranium. Our patient not only had a rare paravertebral mass, but also a skull base mass; this aberrant metastasis may be explained by the role of the vertebral vein system, as described by Batson in 1940 [11].

A few cases of CNS spread have been described. Our patient had signs of compression demanding immediate intervention barring cerebrospinal fluid analysis, and hence the important clinical question about whether or not there was leptomeningeal involvement was left unanswered. There have only been a few cases of leptomeningeal metastasis from prostate cancer reported in the literature [12, 13]. The common signs for leptomeningeal involvement described were lower extremity weakness, neck pain, back pain, and/or sensory loss in a segmental or dermatomal distribution. Of the aforementioned signs, our patient only presented with neck pain. To the best of our knowledge, our case appears to be the first cited case of paravertebral metastasis from prostate cancer. The only mimic in the literature was a case of paravertebral schwannoma simulating prostate cancer metastasis [14].

The medical management for our patient was based on the current standard of care for metastatic prostate cancer. Given his extensive burden of visceral disease from metastases, we offered him systemic chemotherapy with Taxotere for 6 cycles in addition to androgen deprivation therapy (ADT) with leuprolide, based on a study which showed improved overall survival with using both chemotherapy and ADT compared with using ADT alone in patients with progressive androgen-stimulated prostate cancer and distant metastases [15]. Reviewing the literature for novel approaches to treating paravertebral spread did not yield any significantly different options. It did, however, lead to interesting perspectives about the spread of metastatic prostate cancer, specifically to neural structures by way of the spinal veins and plexus.

Conclusion

Paravertebral metastasis is uncommon in prostate cancer, and neurological symptoms such as coughing paroxysms associated with swallowing, as was noted in our patient, may clue one in to the diagnosis. Patients with extensive burden of visceral disease from prostate metastases may benefit from systemic chemotherapy in addition to androgen suppression with leuprolide. Strong consideration should be given to radiation therapy to promote local control where there is concern for cord compression or intractable bony pain.

Acknowledgment

The authors would like to acknowledge the help of Hasan Nabhani, MD, Department of Radiology, Howard University Hospital, and Fasil Tiruneh, MD, Department of Internal Medicine, Howard University Hospital.

Statement of Ethics

The authors have no ethical conflicts to disclose.

Disclosure Statement

The authors have no conflict of interest to declare.

Prostate Cancer Nomograms

If you know anyone with newly diagnosed prostate cancer, here are a few websites featuring nomograms, prediction tools designed to help patients and their physicians understand the nature of their prostate cancer, assess risk based on specific characteristics of a patient and his disease, and predict the likely outcomes of treatment:

http://urology.jhu.edu/prostate/partintables.php

https://www.cancer.duke.edu/Nomogram/

https://www.mskcc.org/nomograms/prostate   – This one has several other useful tools as well.

I hope this is helpful.

Blessings-

Amir Isbell

Breast Cancer Awareness

Breast Cancer is the most common cancer in the world, affecting nearly 12% of all women [1]. Unfortunately, there were 1.7 million new cases of breast cancer diagnosed and 521,000 breast cancer related deaths in 2012 alone [2]. In spite of these facts, a significant amount could be reduced by early detection, via screening mammograms or ultrasounds, and treatment, using various modalities, when available. Such is the case in the United States where breast cancer mortality has decreased by 39% between 1990 and 2015 [3].

If you or a family member ever have the misfortune of being diagnosed with breast cancer, make sure that you have a consult with at least each of the following professionals:

1. Surgical Oncologist
2. Radiation Oncologist
3. Medical Oncologist

Specifically, when you see the radiation oncologist, make sure that you ask about the various radiation therapy schedules such as hypofractionated whole breast irradiation (WBI) and accelerated partial breast irradiation (APBI) as they are now thought to increase survival in resource constrained economies [4].

References

1. McGuire A, Brown JA, Malone C, McLaughlin R, Kerin MJ. Effects of age on the detection and management of breast cancer. Cancers (Basel). 2015 May 22;7(2):908-29.
2. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA: a cancer journal for clinicians. 2015;65(2):87–108.
3. Byers T, Wender RC, Jemal A, Baskies AM, Ward EE, Brawley OW. The American Cancer Society challenge goal to reduce US cancer mortality by 50% between 1990 and 2015: Results and reflections. CA Cancer J Clin. 2016 Sep;66(5):359-69.
4. Khan AJ, Rafique R, Zafar W, Shah C, Haffty BG, Vicini F, Jamshed A, Zhao Y. Nation-Scale Adoption of Shorter Breast Radiation Therapy Schedules Can Increase Survival in Resource Constrained Economies: Results From a Markov Chain Analysis. Int J Radiat Oncol Biol Phys. 2017 Feb 1;97(2):287-295.

Nation-Scale Adoption of Shorter Breast Radiation Therapy Schedules Can Increase Survival in Resource Constrained Economies: Results From a Markov Chain Analysis.

Khan AJ¹, Rafique R², Zafar W³, Shah C⁴, Haffty BG⁵, Vicini F⁶, Jamshed A³, Zhao Y⁷.

Author information

Abstract

PURPOSE:

Hypofractionated whole breast irradiation and accelerated partial breast irradiation (APBI) offer women options for shorter courses of breast radiation therapy. The impact of these shorter schedules on the breast cancer populations of emerging economies with limited radiation therapy resources is unknown. We hypothesized that adoption of these schedules would improve throughput in the system and, by allowing more women access to life-saving treatments, improve patient survival within the system.

METHODS AND MATERIALS:

We designed a Markov chain model to simulate the different health states that a postlumpectomy or postmastectomy patient could enter over the course of a 20-year follow-up period. Transition rates between health states were adapted from published data on recurrence rates. We used primary data from a tertiary care hospital in Lahore, Pakistan, to populate the model with proportional use of mastectomy versus breast conservation and to estimate the proportion of patients suitable for APBI. Sensitivity analyses on the use of APBI and relative efficacy of APBI were conducted to study the impact on the population.

RESULTS:

The shorter schedule resulted in more women alive and more women remaining without evidence of disease (NED) compared with the conventional schedule, with an absolute difference of about 4% and 7% at 15 years, respectively. Among women who had lumpectomies, the chance of remaining alive and with an intact breast was 62% in the hypofractionation model and 54% in the conventional fractionation model.

CONCLUSIONS:

Increasing throughput in the system can result in improved survival, improved chances of remaining without evidence of disease, and improved chances of remaining alive with a breast. These findings are significant and suggest that adoption of hypofractionation in emerging economies is not simply a question of efficiency and cost but one of access to care and patient survivorship.

 

Blessings,

Amir Isbell