This document provides an overview of breast anatomy, physiology, pathology, and cancer. It describes the gross and microscopic anatomy of the breast and discusses lactation physiology. It then covers breast cancer risk factors, types including ductal carcinoma in situ and invasive ductal carcinoma, genetics, staging, diagnosis, screening guidelines, and treatment options including surgery, chemotherapy, radiation, hormone, and targeted therapies. Key points include that breast cancer is the most common cancer in women, risk increases with age and estrogen exposure, staging guides treatment, and treatment involves a multidisciplinary approach.
science has an evolving nature. what happened today may not be tomorrow, what is not today may happen tomorrow.
No one is complete so reading and thinking may open the door to the hidden ground.
TEGENE ALEMU CANCER BIOLOGY SURGERY DEPARTMENTTegeneAlemu
Cancer Biology by Tegene Alemu Jimma Ethiopia
Surgery Role on Oncology
On this seminar
Hallmark of cancer
Cell cycles
Apoptosis of cell
Diagnosis
Therapy
breast is the mammary gland with lobes and ductules with lactiferous ducts.
it extends from 2nd intercostal to 6 intercostal ribs and lies over pectoralis major muscle
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
science has an evolving nature. what happened today may not be tomorrow, what is not today may happen tomorrow.
No one is complete so reading and thinking may open the door to the hidden ground.
TEGENE ALEMU CANCER BIOLOGY SURGERY DEPARTMENTTegeneAlemu
Cancer Biology by Tegene Alemu Jimma Ethiopia
Surgery Role on Oncology
On this seminar
Hallmark of cancer
Cell cycles
Apoptosis of cell
Diagnosis
Therapy
breast is the mammary gland with lobes and ductules with lactiferous ducts.
it extends from 2nd intercostal to 6 intercostal ribs and lies over pectoralis major muscle
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
2. • To have a review of on the Basic and Clinical Sciences in
relation to Breast Cancer with emphasis on the
diagnosis and management of the disease
OBJECTIVE
13. GROSS ANATOMY
Batson’s vertebral venous plexus
invests the vertebrae
from base of skull to sacrum
metastases to vertebrae, skull,
pelvic bones and CNS
14. GROSS ANATOMY
Lateral cutaneous branches
of 3rd – 6th intercostal nerves
Cutaneous branches from
Supraclavicular nerve
Intercostobrachial nerve
15. GROSS ANATOMY
Axillary vein group
4-6 lymph nodes
medial or posterior
to the vein
receives most of the
lymph drainage from
upper extremity
16. GROSS ANATOMY
External mammary grou
5-6 lymph nodes
lower border of
pectoralis minor
contiguous with late
thoracic vessels
27. PHYSIOLOGY
COLOSTRUM
- produced during the first few days after birth
- rich in cells (lymphocytes, monocytes ), lactalbumin, fat -soluble vitamins, &
minerals and contains lgA
MILK
- secreted by the third or fourth day after birth
- consists of proteins (caseins, IgA, lactalbumin), many lipid droplets, & lactose
- released from the mammary glands via the milk ejection reflex
SECRETIONS OF MAMMARY GLAND
28. PHYSIOLOGY
PROLACTIN
- is the major hormone responsible for lactogenesis
- is structurally homologous to growth hormone
Actions:
1. Stimulates milk production in the breast
2. Stimulates breast development
3. Inhibits ovulation by decreasing synthesis and release of gonadotropin-
releasing hormone (GnRH)
4. Inhibits spermatogenesis (by decreasing GnRH)
29. PHYSIOLOGY
Regulation of Secretion:
Hypothalamic control by dopamine and thyrotropin-releasing hormone (TRH)
- tonically inhibited by dopamine (prolactin-inhibiting factor [PIF])
- TRH increases prolactin secretion.
Negative feedback control
- inhibits its own secretion by stimulating the hypothalamic release of
dopamine
31. BREAST CANCER
• a malignant proliferation of epithelial cells lining the ducts or lobules of the
breast
• Epithelial malignancies of the breast are the most common cause of cancer in
women (excluding skin cancer), accounting for about one third of all cancer in
women.
• Breast cancer is the most common non-skin malignancy in women and the second
most common cause of cancer deaths.
• The most important risk factors are estrogenic stimulation and age.
• All cancers arise by the accumulation of DNA alterations and epigenetic
changes.
• Tumorigenesis also requires changes in the normal supporting cells—alteration of
the normal crosstalk and function of stromal cells may be an important
determinant of stromal invasion.
32. BREAST CANCER
• the most common cause of a breast mass in postmenopausal patients
• occurs most frequently in the upper outer quadrant of the breast
• metastasis include axillary lymph nodes, lung, liver, and bone
33. RISK FACTORS
Germ line
mutations
First-degree
relatives with
breast cancer
Race/Ethnicity
Age
Age at Menarche
Age at first live
Estrogen Exposure
Breast density
Radiation
Exposure
Diet
Obesity
Exercise
Breastfeeding
Environmental
34. GENETICS
• Familial – 8-10% of breast cancer
• BRCA-1 (maps to chromosome 17q21) mutations account for about 5%.
• BRCA-1 - involved in transcription coupled DNA repair; an increased risk of
ovarian cancer in women and prostate cancer in men
• BRCA-2 on chromosome 11 may account for 2–3% of breast cancer; Mutations
are associated with an increased risk of breast cancer in men and women.
• Germ-line mutations in p53
• Germ-line mutations in PALB2, hCHK2, and PTEN
• Sporadic breast cancers
• overexpression of HER2/neu in 25% of cases
• p53 mutations in 40%
• loss of heterozygosity at other loci
36. BREAST CANCER TYPES
1. Ductal Carcinoma-In-Situ
a. Comedo Carcinoma
b. Non-Comedo
2. Lobular Carcinoma-In-Situ
3. Invasive Ductal Carcinoma
4. Invasive Lobular Carcinoma
5. Medullary Carcinoma
6. Mucinous (Colloid) Carcinoma
7. Tubular Carcinoma
37. 1. Ductal Carcinoma-In-Situ
• Neoplastic lesions where cells are limited to ducts by the
basement membrane
• Frequently presents as mammographic calcifications
• Myoepithelial cells are preserved
• With microinvasion and atypia
Sub-types:
a. Comedo Carcinoma
b. Non-Comedo
38. a. Comedo Ductal Carcinoma-In-Situ
O High-grade DCIS
O Center: nidus of necrosis
39. b. Non-Comedo
1. CRIBRIFORM - cookie-cutter like appearance
2. PAPILLARY- papillary fronds with
fibrovascular core
3. MICROPAPILLARY- Papillary fronds
emanating from the fronds, no fibrovascular
40. b. Non-Comedo
1. CRIBRIFORM - cookie-cutter like appearance
2. PAPILLARY- papillary fronds with
fibrovascular core
3. MICROPAPILLARY- Papillary fronds
emanating from the fronds, no fibrovascular
41. b. Non-Comedo
1. CRIBRIFORM - cookie-cutter like appearance
2. PAPILLARY- papillary fronds with
fibrovascular core
3. MICROPAPILLARY- Papillary fronds
emanating from the fronds, no fibrovascular
42. b. Non-Comedo
1. CRIBRIFORM - cookie-cutter like appearance
2. PAPILLARY- papillary fronds with
fibrovascular core
3. MICROPAPILLARY- Papillary fronds
emanating from the fronds, no fibrovascular
44. 3. Invasive ductal carcinoma
• Firm and hard with an irregular border
• Produce a grating sound when cut or scraped
• Microscopic:
45. 4. Invasive lobular carcinoma
• Palpable mass
• Greater incidence or bilateral
• Histologic:
Indian file pattern – discohesive
infiltrating tumor cells arranged in
a file
• E-cadherin mutation – causes
formation of discohesive cells
46. 5. Medullary Carcinoma
• Soft, fleshy, well defined mass
• Better prognosis
• Histologic: Solid syncytium-like
sheets of large cells with vesicular
nuclei and prominent nucleoli
• Moderate to marked
lymphoplasmacytic infiltrate
surrounding the tumor
• Pushing borders
• Poor differentiation
47. 6. Mucinous (colloid) carcinoma
• Small islands of cells within large lakes
of mucus
• Seen in older women
• Very good prognosis
• Pale gray-blue gelatin mucinous
substance
51. GENE EXPRESSION SUBTYPES
TYPES /
IMMUNOSTAIN RESULT
CHARACTERISTICS
Luminal A
ER +, PR +, HER2NEU -
Express cytokeratins 8 and 18, have the highest levels of estrogen receptor expression, tend to be low
grade, are most likely to respond to endocrine therapy, and have a favorable prognosis, tend to be less
responsive to chemotherapy.
Luminal B
ER +, PR +, HER2NEU -
Tumor cells are also of luminal epithelial origin, but with a gene expression pattern distinct from luminal
luminal A. Prognosis is somewhat worse that luminal A.
HER2 amplified
ER -, PR -, HER2NEU +
These tumors have amplification of the HER2 gene on chromosome 17q and frequently exhibit
coamplification and overexpression of other genes adjacent to HER2. Historically the clinical prognosis of
such tumors was poor. However, with the advent of trastuzumab and other targeted therapies the clinical
outcome of HER2-positive patients is markedly improving.
Basal
ER -, PR -, HER2NEU -
These estrogen receptor/progesterone receptor–negative and HER2 -negative tumors (so-called triple
triple negative) are characterized by markers of basal/myoepithelial cells. They tend to
be high grade, and express cytokeratins 5/6 and 17 as well as vimentin, p63, CD10, a-smooth muscle
actin, and epidermal growth factor. Patients with BRCA mutations also fall within this molecular subtype.
They also have stem cell characteristics.
Normal breast–like Gene expression profile reminiscent of nonmalignant “normal” breast epithelium. Prognosis is similar to
to the luminal B group. Somewhat controversial and may represent contamination of the sample by
normal mammary epithelium.
60. • NON-INVASIVE BREAST CANCER
• Ductal Carcinoma In-Situ
• Surgery + Radiation Therapy + Tamoxifen
• Lobular Carcinoma In-Situ
• may be a premalignant lesion
• treated with an SERM or an aromatase inhibitor for 5 years
• Semi-annual – Physical examination
• Annual - Mammography
TREATMENT
61. • INVASIVE BREAST CANCER
• Operable (Stage I and II)
• Locally advanced (Stage III)
• Metastatic (Stage IV)
TREATMENT
67. • INVASIVE BREAST CANCER
• Locally Advanced
• Neoadjuvant Combination Chemotherapy (Cyclophosphamide, Doxorubicin, 5-
Fluorouracil) for monthly cycle, 6 cycles → Surgery → Radiation Therapy
TREATMENT
68. • INVASIVE BREAST CANCER
• Metastatic Disease
• Depends on ER/PR status and treatment philosophy
• No therapy is known to cure patients
• Median survival: 22 months with conventional treatment
• Aromatase Inhibitor: ER/PR positive
• Combination Chemotherapy: ER/PR negative
• Trastuzumab: HER2NEU positive
TREATMENT
70. • RADICAL MASTECTOMY by HALSTED
• extensive surgical removal of the breast and its related structures, including
the pectoralis major and minor muscles, axillary lymph nodes and fascia, and
and part of the thoracic wall.
• MODIFIED RADICAL MASTECTOMY
• PATEY’S OPERATION - excision of the entire breast and axillary lymph nodes
(I-III) and minor muscles, with preservation of the pectoralis major
• SCANLON’S OPERATION – Pectoralis minor incised; Level III LN removed
• AUCHINLONCLOSS’ OPERATION – Pectoralis minor left intact, Level III LN not
removed
• LUMPECTOMY (TYLECTOMY)
• surgical excision of only the palpable mass.
SURGERY
72. PHARMACOLOGY
STAGE I & II DISEASE
(6) CMF protocol
cyclophosphamide
methotrexate
fluorouracil
(6) FAC protocol
fluorouracil
doxorubicin
cyclophosphamide
73. PHARMACOLOGY
STAGE I & II DISEASE
(6) FEC protocol
fluorouracil
epirubicin
cyclophosphamide
(4) cycles of doxorubicin
cyclophosphamide
74. PHARMACOLOGY
SUBCLASS/DRUG MOA
ACUTE
TOXICITIES
CHRONIC TOXICITIES
Alkylating agent
Cyclophosphamide
Forms DNA cross-links, resulting in inhibition
of DNA synthesis and function
Nausea,
vomiting
Myelosuppression,
alopecia, hemorrhagic
cystitis
Antimetabolite
Methotrexate
Inhibits DHFR, resulting in inhibition of
synthesis of thymidylate, purine nucleotides,
serine, and methionine
Mucositis,
diarrhea
Myelosuppression
Antimetabolite
5-Fluorouracil
Inhibits thymidylate synthase, and its
metabolites are incorporated into RNA and
DNA, all resulting in inhibition of DNA
synthesis and function and in RNA processing
Nausea,
mucositis,
diarrhea
Myelosuppression,
neurotoxicity
Anthracycline
Doxorubicin
Epirubicin
Oxygen free radicals bind to DNA causing
strand breakage; inhibits topoisomerase II;
intercalates into DNA
Nausea,
arrhythmias
Alopecia, myelosuppres
sion, cardiomyopathy,
myelosuppression
76. PHARMACOLOGY
STAGE I & II DISEASE
TRASTUZUMAB
• monoclonal antibody against the HER-2/ neu
receptor
• added to anthracycline- and taxane-containing
adjuvant chemotherapy
• for women with HER-2-overexpressing breast cancer
77. PHARMACOLOGY
STAGE I & II DISEASE
TAMOXIFEN
• beneficial in postmenopausal women when used
alone or in combination with cytotoxic
chemotherapy
• present recommendation is to administer
tamoxifen for 5 years of continuous therapy after
surgical resection
78. PHARMACOLOGY
SUBCLASS/DRUG MOA
ACUTE
TOXICITIES
CHRONIC TOXICITIES
Growth factor
receptor inhibitor
Trastuzumab
Inhibits the binding of EGF to the HER-2/neu
growth receptor
Nausea,
vomiting,
chills, fever,
headache
Cardiac dysfunction
Antiestrogen/SERM
Tamoxifen
Estrogen antagonist actions in breast tissue
and CNS, estrogen agonist effects in liver and
bone
Hot flushes, thromboembolism,
endometrial hyperplasia
80. PREVENTION
• With Breast Cancer – 0.5% per year risk of developing
second breast cancer
• Increased Risk of Breast Cancer
• Reduce risk by 49% by taking Tamoxifen or an
Aromatase inhibitor for 5 years
• With BRCA-1 mutation
• Reduce risk by 90% with Simple Mastectomy
Editor's Notes
Carcinoma of the breast is the most common non-skin malignancy in women and is second only to lung cancer as a cause of cancer deaths.
The breast is composed of *15 to 20 lobes, which are each *composed of several lobules
Cooper’s suspensory ligaments which are *fibrous bands of connective tissue travel through the breast, *insert perpendicularly into the dermis, and *provide structural support.
The mature female breast extends from the level of the second or third rib to the inframammary fold at the sixth or seventh rib. It extends transversely from the lateral border of the sternum to the anterior axillary line.
The deep or posterior surface of the breast rests on the fascia of the pectoralis major, serratus anterior, and external oblique abdominal muscles, and the upper extent of the rectus sheath.
The retromammary bursa may be identified on the posterior aspect of the breast between the investing fascia of the breast and the fascia of the pectoralis major muscles.
The axillary tail of Spence extends laterally across the anterior axillary fold. The upper outer quadrant of the breast contains a greater volume of tissue than do the other quadrants.
The breast receives its principal blood supply from: *(a) perforating branches of the internal mammary artery; *(b) lateral branches of the posterior intercostal arteries; and *(c) branches from the axillary artery, including the *highest thoracic, *lateral thoracic, and *pectoral branches of the thoracoacromial artery (Fig. 17-5).
The second, third, and fourth anterior intercostal perforators and branches of the internal mammary artery arborize in the breast as the medial mammary arteries. The lateral thoracic artery gives off branches to the serratus anterior, pectoralis major and pectoralis minor, and subscapularis muscles. It also gives rise to lateral mammary branches.
The veins of the breast and chest wall follow the course of the arteries, with venous drainage being toward the axilla. The three principal groups of veins are: *(a) perforating branches of the internal thoracic vein, (b) perforating branches of the posterior intercostal veins, and *(c) tributaries of the axillary vein..
Batson’s vertebral venous plexus, which invests the vertebrae and extends from the base of the skull to the sacrum, may provide a route for breast cancer metastases to the vertebrae, skull, pelvic bones, and central nervous system
Lateral cutaneous branches of the third through sixth intercostal nerves provide sensory innervation of the breast (lateral mammary branches) and of the anterolateral chest wall.
Cutaneous branches that arise from the cervical plexus, specifically the anterior branches of the supraclavicular nerve, supply a limited area of skin over the upper portion of the breast.
The intercostobrachial nerve is the lateral cutaneous branch of the second intercostal nerve and may be visualized during surgical dissection of the axilla. Resection of the intercostobrachial nerve causes loss of sensation over the medial aspect of the upper arm.
Lymph vessels generally parallel the course of blood vessels. The boundaries for lymph drainage of the axilla are not well demarcated, and there is considerable variation in the position of the axillary lymph nodes. The six axillary lymph node groups recognized by surgeons are:
the axillary vein group (lateral), which consists of four to six lymph nodes that lie medial or posterior to the vein and receive most of the lymph drainage from the upper extremity;
the external mammary group (anterior or pectoral group), which consists of five to six lymph nodes that lie along the lower border of the pectoralis minor muscle contiguous with the lateral thoracic vessels and receive most of the lymph drainage from the lateral aspect of the breast;
the central group, which consists of three or four sets of lymph nodes that are embedded in the fat of the axilla lying immediately posterior to pectoralis minor muscle and receive lymph drainage both from the axillary vein, external mammary, and scapular groups of lymph nodes, and directly from the breast;
the scapular group (posterior or subscapular), which consists of five to seven lymph nodes that lie along the posterior wall of the axilla at the lateral border of the scapula contiguous with the subscapular vessels and receive lymph drainage principally from the lower posterior neck, the posterior trunk, and the posterior shoulder
the subclavicular group (apical), which consists of six to twelve sets of lymph nodes that lie posterior and superior to the upper border of the pectoralis minor muscle and receive lymph drainage from all of the other groups of axillary lymph nodes
the interpectoral group (Rotter’s lymph nodes), which consists of one to four lymph nodes that are interposed between the pectoralis major and pectoralis minor muscles and receive lymph drainage directly from the breast.
The lymph node groups are assigned levels according to their anatomic relationship to the pectoralis minor muscle. *Lymph nodes located lateral to or below the lower border of the pectoralis minor muscle are referred to as level I lymph nodes, which include the axillary vein, external mammary, and scapular groups. *Lymph nodes located superficial or deep to the pectoralis minor muscle are referred to as level II lymph nodes, which include the central and interpectoral groups. *Lymph nodes located medial to or above the upper border of the pectoralis minor muscle are referred to as level III lymph nodes, which consist of the subclavicular group.
LOBE: 10 in whole breast
LOBULE: many per lobule
ACINUS: may per lobule
DUCT: intra- or inter- lobular, lead to lactiferous ducts of
Nipple
So the breast is fatty / fibrofatty and glandular
ACINUS- Histologically the smallest
component)
Composed of two cell layers:
Myoepithelial cell:
Actin, weak S-100 (immunostains)
Not easily identified in H&E; needs immunostain
Breached during cancer
Luminal/glandular epithelial cell:
EMA, keratin, milk fat globule membrane, alpha lactalbumin
100 (immunostains)
INTERLOBULAR: dense fibrous connective tissues admixed with fatty tissue
INTRALOBULAR: Loose fibrous CT, hormonally-responsive fibroblast-like cells admixed with scattered lymphocytes
RESTING: 50:50 gland and stroma ration
Resting mammary glands are composed of lactiferous sinuses and ducts lined in most areas
by a stratified cuboidal epithelium, with a basal layer consisting of scattered myoepith e l i a l
c e l ls.
A basal lamina separates the epithelial components from the underlying stroma.
LACTATING: glands predominate over stroma
mammary g l ands are enlarged during pregnancy by the development of a lveo l i .
1 . Alveolar c e l l s (secretory cells) (Figure 19.6)
a . Alveolar cells line the alveoli of active mammary glands and are surrounded by an
incomplete layer of myoepith e l i a l cells.
b. They are richly endowed with RER a n d contain several Golgi complexes, numerous
mitochondria, lipid droplets, and vesicles containing milk protein (caseins) and lactose.
ATROPHIC: stroma predominates over glands
In puberty, estrogen and progesterone contribute to the development of the breast
D . Secretions o f t h e mammary g l a nds
1. Colostrum (prote i n-rich yel lowish fluid)
a. Colostrum is produced during the first few days after birth.
b. It is rich in cells (lymphocytes, monocytes ), lactalbumin, fat -soluble vitamins, and minerals
and contains immunog l o b u l i n A ( l gA).
2. M i l k
a. Milk begins t o b e secreted b y the third or fourth day after birth.
b. Milk consists of proteins (caseins, IgA, lactalbumin), many lipid droplets, and lactose.
c. It is released from the mammary glands via the m i l k ejection reflex in response to a variety
of external stimuli related to suckling. The milk ej ection reflex involves release of oxytoc i n
(from axons i n the pars nervosa of the pituitary gland), which induces contraction of the
myoepith e l i a l cel ls, forcing milk into the larger ducts and out of the breast.
Prolactin
■■ is the major hormone responsible for lactogenesis.
■■ participates, with estrogen, in breast development.
■■ is structurally homologous to growth hormone.
Actions of prolactin
(1) Stimulates milk production in the breast (casein, lactalbumin)
(2) Stimulates breast development (in a supportive role with estrogen)
(3) Inhibits ovulation by decreasing synthesis and release of gonadotropin-releasing
hormone (GnRH)
(4) Inhibits spermatogenesis (by decreasing GnRH)
a. R egulation of prolactin secretion (Figure 7.7 and Table 7.3)
(1) Hypothalamic control by dopamine and thyrotropin-releasing hormone (TRH)
■■ Prolactin secretion is tonically inhibited by dopamine (prolactin-inhibiting factor
[PIF]) secreted by the hypothalamus. Thus, interruption of the hypothalamic–
pituitary tract causes increased secretion of prolactin and sustained lactation.
■■ TRH increases prolactin secretion.
(2) Negative feedback control
■■ Prolactin inhibits its own secretion by stimulating the hypothalamic release of
dopamine.
Risk Factors. Beyond female sex, the major risk factors are related to hereditary factors, lifetime exposure to estrogen and, to a lesser extent,
environmental or lifestyle factors. Among the large number of identified risk factors are the following:
About 15% to 20% of women with breast cancer have an affected first degree relative (mother, sister, or daughter),
Non-Hispanic white women have the highest incidence
risk rises throughout a woman’s lifetime, peaking at 70 to 80 years
Menarche at ages younger than 11 years increases risk by 20%
Age at first live birth. A full-term pregnancy before the age of 20 halves the risk
Estrogen exposure. Menopausal hormone therapy increases the risk of breast cancer, particularly when estrogen and a progestin are given together for a period of years.
Breast density. Women with very dense breasts on mammography have a four- to six-fold higher risk
OBESITY which is attributed to the synthesis of estrogens in fat depots.
Exercise. There is a probable small protective effect
Breastfeeding. The longer women breastfeed, the greater the reduction in risk.
Env Toxins definitive associations have yet to be made.
Perhaps 8–10% of breast cancer is familial. BRCA-1 mutations account for about 5%.
BRCA-1 maps to chromosome 17q21 and appears to be involved in transcription coupled
DNA repair. Ashkenazi Jewish women have a 1% chance of having a
common mutation (deletion of adenine and guanine at position 185). The BRCA-1
syndrome includes an increased risk of ovarian cancer in women and prostate cancer
in men. BRCA-2 on chromosome 11 may account for 2–3% of breast cancer.
Mutations are associated with an increased risk of breast cancer in men and women.
Germ-line mutations in p53 (Li-Fraumeni syndrome) are very rare, but breast cancer,
sarcomas, and other malignancies occur in such families.
Germ-line mutations in PALB2, hCHK2, and PTEN may account for some familial breast cancer.
Sporadic breast cancers show many genetic alterations, including overexpression of HER2/
neu in 25% of cases, p53 mutations in 40%, and loss of heterozygosity at other loci.
Major pathways of breast cancer development. Three main pathways have been identified. The most common pathway (yellow arrow) leads to ER positive carcinomas. Recognizable precursor lesions include flat epithelial atypia nad atypical hyperplasia. A less common pathway (blue arrow) leads to carcinomas that are negative for ER and HER2. The box with a question mark indicates that no precursor lesion have been identified perhaps lesions progress quickly to carcinoma. The third pathway (green arrow) consist of HER2 positive concers which may be ER positive or negative. Amlification of the HER2 gene is also presnt in a subset of atypical apocrine lesions, which may represent a precursor lesion. Each molecular subtype has a characteristic gene expression profile termed luminal.
DCIS is a malignant clonal proliferation of epithelial cells limited to ducts and lobules by the basement membrane. The term “ductal” was used to describe this
lesion because when it involves lobules, the expanded acini take on an appearance resembling small ducts. Myoepithelial cells are preserved in involved ducts/lobules, although
they may be diminished in number. DCIS can spread throughout the ductal system and produce extensive lesions involving an entire sector of a breast.
DCIS can be divided into two major architectural subtypes, comedo and noncomedo
Comedo DCIS may occasionally produce vague nodularity, but more often it is detected on mammography as clustered or linear and branching areas of calcification (Fig. 23-17A). It is
defined by two features: (1) tumor cells with pleomorphic, highgrade nuclei and (2) areas of central necrosis (Fig. 23-17B).
Noncomedo DCIS lacks either high-grade nuclei or central necrosis. Several patterns may be seen.
Cribriform DCIS may have rounded (cookie cutter–like) spaces (Fig. 23-17C) within the ducts, or a solid DCIS pattern.
DCIS produces true papillae with fibrovascular cores that lack a myoepithelial cell layer.
Micropapillary DCIS produces bulbous protrusions without a fibrovascular core, often arranged in complex intraductal patterns
LCIS is a clonal proliferation of cells within ducts and lobules that grow in a discohesive fashion, usually due
to an acquired loss of the tumor suppressive adhesion protein E-cadherin.
Invasive carcinomas can be divided based on molecular and morphologic characteristics into several clinically important subgroups.
Women should be strongly encouraged to examine their breasts monthly. In premenopausal women, questionable or nonsuspicious (small) masses should be reexamined in 2–4 weeks (Fig. 70-1). A mass in a premenopausal woman that persists throughout her cycle and any mass in a postmenopausal woman
should be aspirated.
If the mass is solid, the pt should undergo a mammogram and
excisional biopsy.
If the mass is a cyst filled with nonbloody fluid that goes away
with aspiration, the pt is returned to routine screening. If the cyst aspiration leaves
a residual mass or reveals bloody fluid, the pt should have a mammogram and
excisional biopsy.
Risk defined using online tools like the modified gail model.
Screening mammograms performed every other year beginning at age 50 years have been shown to save lives.
standard treatment for this disease was mastectomy.
However, treatment of this condition by lumpectomy and radiation
therapy gives survival that is as good as the survival for invasive
breast cancer treated by mastectomy. Addition of tamoxifen to any DCIS surgical/radiation
therapy regimen further improves local control.
lobular neoplasia may be a premalignant lesion that
suggests an elevated risk of subsequent breast cancer, rather than a
form of malignancy itself, and aggressive local management seems
unreasonable. Most patients should be treated with an SERM or an
aromatase inhibitor (for postmenopausal women) for 5 years and followed with careful annual mammography and semiannual physical
examinations.
Ductal carcinoma in situ is noninvasive tumor present in the breast ducts.
Treatment of choice is wide excision with breast radiation therapy. In one study,
adjuvant tamoxifen further reduced the risk of recurrence.
Invasive breast cancer can be classified as operable, locally advanced, and
metastatic. In operable breast cancer, the outcome of primary therapy is the same
with modified radical mastectomy or lumpectomy followed by breast radiation
therapy. Axillary dissection may be replaced with sentinel node biopsy to evaluate
node involvement. The sentinel node is identified by injecting a dye in the tumor
site at surgery; the first node in which dye appears is the sentinel node. Women
with tumors <1 cm and negative axillary nodes require no additional therapy
beyond their primary lumpectomy and breast radiation. Adjuvant combination
chemotherapy for 6 months appears to benefit premenopausal women with positive
lymph nodes, pre- and postmenopausal women with negative lymph nodes
but with large tumors or poor prognostic features, and postmenopausal women
with positive lymph nodes whose tumors do not express estrogen receptors.
Estrogen receptor–positive tumors >1 cm with or without involvement of lymph
nodes are treated with aromatase inhibitors. Women who began treatment with
tamoxifen before aromatase inhibitors were approved should switch to an aromatase
inhibitor after 5 years of tamoxifen and continue for another 5 years.
Adjuvant chemotherapy is added to hormonal therapy in estrogen receptor–
positive, node-positive women and is used without hormonal therapy in estrogen
receptor–negative node-positive women, whether they are pre- or postmenopausal.
Various regimens have been used. The most effective regimen appears to
be four cycles of doxorubicin, 60 mg/m2, plus cyclophosphamide, 600 mg/m2, IV
on day 1 of each 3-week cycle followed by four cycles of paclitaxel, 175 mg/m2, by
3-h infusion on day 1 of each 3-week cycle. In women with HER2+ tumors, trastuzumab
augments the ability of chemotherapy to prevent recurrence. The activity
of other combinations is being explored. In premenopausal women, ovarian
ablation (e.g., with the luteinizing hormone–releasing hormone [LHRH] inhibitor
goserelin) may be as effective as adjuvant chemotherapy.
Tamoxifen adjuvant therapy (20 mg/d for 5 years) or an aromatase inhibitor
(anastrozole, letrozole, exemestane) is used for postmenopausal women with
tumors expressing estrogen receptors whose nodes are positive or whose nodes are
negative but with large tumors or poor prognostic features. Breast cancer will recur
in about half of pts with localized disease. High-dose adjuvant therapy with marrow
support does not appear to benefit even women with high risk of recurrence.
Pts with locally advanced breast cancer benefit from neoadjuvant combination
chemotherapy (e.g., CAF: cyclophosphamide 500 mg/m2, doxorubicin 50 mg/m2,
and 5-fluorouracil 500 mg/m2 all given IV on days 1 and 8 of a monthly cycle for 6
cycles) followed by surgery plus breast radiation therapy.
Treatment for metastatic disease depends on estrogen receptor status and
treatment philosophy. No therapy is known to cure pts with metastatic disease.
Median survival is about 22 months
with conventional treatment: aromatase inhibitors for estrogen receptor–positive
tumors and combination chemotherapy for receptor-negative tumors. Pts whose
tumors express HER2/neu have higher response rates by adding trastuzumab
(anti-HER2/neu) to chemotherapy. Trastuzumab emtansine is a drug conjugate that
targets HER2-expressing cells and has antitumor activity. Some advocate sequential
use of active single agents in the setting of metastatic disease. Active agents
in anthracycline- and taxane-resistant disease include capecitabine, vinorelbine,
gemcitabine, irinotecan, and platinum agents. Pts progressing on adjuvant tamoxifen
may benefit from an aromatase inhibitor such as letrozole or anastrozole. Half
of pts who respond to one endocrine therapy will respond to another. Bisphosphonates
reduce skeletal complications and may promote antitumor effects of other
therapy. Radiation therapy is useful for palliation of symptoms.
Radical mastectomy is the extensive surgical removal of the breast and its
related structures, including the pectoralis major and minor muscles, axillary
lymph nodes and fascia, and part of the thoracic wall.
It may injure the long thoracic and thoracodorsal
nerves and may cause postoperative swelling (edema) of the upper limb as a result of lymphatic
obstruction caused by the removal of most of the lymphatic channels that drain the arm or by
venous obstruction caused by thrombosis of the axillary vein.
Modifi ed radical mastectomy involves excision of the entire breast and axillary lymph nodes,
with preservation of the pectoralis major and minor muscles. (The pectoralis minor muscle is usually
retracted or severed near its insertion into the coracoid process.)
Lumpectomy (tylectomy) is the surgical excision of only the palpable mass in carcinoma of the
breast.
In this situation, postoperative use of systemic adjuvant chemotherapy with six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF protocol) or of fluorouracil, doxorubicin, and cyclophosphamide (FAC) has been shown to significantly reduce the relapse rate and prolong survival.
Alternative regimens with equivalent clinical benefit include four cycles of doxorubicin and cyclophosphamide and six cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC). Each of these chemotherapy regimens has benefited women with stage II breast cancer with one to three involved lymph nodes.
Women with four or more involved nodes have had limited benefit thus far from adjuvant chemotherapy. Long-term analysis has clearly shown improved survival rates in node-positive premenopausal women who have been treated aggressively with multiagent combination chemotherapy. The results from three randomized clinical trials clearly show that the addition of trastuzumab, a monoclonal antibody directed against the HER-2/ neu receptor, to anthracycline- and taxane-containing adjuvant chemotherapy benefits women with HER-2-overexpressing breast cancer with respect to disease-free and overall survival.
Breast cancer was the first neoplasm shown to be responsive to hormonal manipulation. Tamoxifen is beneficial in postmenopausal women when used alone or in combination with cytotoxic chemotherapy. The present recommendation is to administer tamoxifen for 5 years of continuous therapy after surgical resection. Longer durations of tamoxifen therapy do not appear to add additional clinical benefit. Postmenopausal women who complete 5 years of tamoxifen therapy should be placed on an aromatase inhibitor such as anastrozole for at least 2.5 years, although the optimal duration is unknown. In women who have completed 2–3 years of tamoxifen therapy, treatment with an aromatase inhibitor for a total of 5 years of hormonal therapy is now recommended (see Chapter 40 ). Results from several randomized trials for breast cancer have established that adjuvant chemotherapy for premenopausal women and adjuvant tamoxifen for postmenopausal women are of benefit to women with stage I (node-negative) breast cancer. While this group of patients has the lowest overall risk of recurrence after surgery alone (about 35–50% over 15 years), this risk can be further reduced with adjuvant therapy.
The most important prognostic variables are provided by tumor staging. The size of the tumor and the status of the axillary lymph nodes provide reasonably accurate information on the likelihood of tumor relapse. The relation of pathologic stage to 5-year survival is shown in the table.
Women with breast cxancer have 0.5 % per year risk of developing a second breast cancer. Women at risk of breast cancer can reduce their risk by 49% by taking tamoxifen or an aromatase inhibitor for 5 years. Women with BRCA 1 mutations can reduce the risk by 90% with simple mastectomy.