The SPPiRE trial is a cluster randomized controlled trial that aims to assess the effectiveness of a web guided medication review in reducing potentially inappropriate prescribing and polypharmacy in older patients taking many medications in Irish primary care. General practices are randomized to either the intervention of a web guided medication review plus training or usual GP care. The primary outcomes are the number of repeat medications and proportion of patients with at least one potentially inappropriate prescription. Secondary outcomes include quality of life, treatment burden, attitudes to deprescribing and healthcare utilization.

1. Criteria I – Introduction (4 points)
1. Describe the common complaint/problem selected- breast
cancer
2. Discuss the pathophysiology of the common
complaint/problem.
3. Detail the necessary review of systems and what would be
seen on physical examination for this complaint/problem.
4. Provide rationale from the literature to support your work.
In the United State, breast cancer is the leading cause of
cancer death among female. Breast cancer ranks second (after
lung cancer) as a cause of cancer death in women. In 2016,
around 245, 229 new cases of female breast cases reported, and
41,487 women died of this disease (CDC, 2019). In 2018,
approximately 63,960 cases of in situ disease and 266,120 cases
of invasive disease were diagnosed.1 About 40,920 breast
cancer-related deaths occurred in 2018, which represents 6.7%
of all cancer-related deaths.2 Female breast cancer is most
common in middle-aged and older women; median age at
diagnosis is 62 years.2 In 2016, more than 3.5 mil- lion women
were breast cancer survivors.3 The lifetime risk of developing
breast cancer in the United States is 12.4% (1 in 8 women ).
(ACS, 2019)
Breast cancer mortality was 41% higher among black women
(29.2 deaths per 100,000 population) than white women (20.6
deaths per 100,000 population). Breast cancer death rates
decreased during 2010–2014 among both blacks and whites,
although differences in trends by race and age were found.
Overall, breast cancer death rates decreased faster among white
women (-1.9% per year) compared with black women (-1.5% per

2. year). Among women aged <50 years, breast cancer death rates
decreased at the same pace among black and white women,
whereas white women aged ≥50 years had significantly larger
decreases. The largest difference by race was observed among
women aged 60–69 years: breast cancer death rates decreased
2.0% per year among white women compared with 1.0% among
black women. Death rates from breast cancer have been
declining since about 1990, in part due to better screening and
early detection, increased awareness, and continually
improving treatment options, decline in prescriptive hormone
replacement therapy after menopause. (ACS, 2019).
Breast cancer is a disease in which cells in the breast grow out
of control. The majority of breast cancers (95%) are sporadic;
only a small proportion, particularly those diagnosed in young
women, are due to a highly penetrant autosomal-dominant trait.
Over the past 5 years there has been consider- able progress in
the identification and localization of the genes responsible for
hereditary breast cancer. Two in particular have grabbed the
headlines; these are BRCA1 and BRCA2. Subtypes of breast
cancer include those driven by specific hormones, such as
estrogen, progestogen or the protein HER2. Sixty percent of
breast cancers are estrogen positive. Twenty percent of breast
cancers are HER2-positive. Another 20 percent are triple-
negative breast cancers, a type of breast cancer that tests
negative for estrogen, progesterone and HER2. Triple-negative
breast cancer is among the more aggressive forms of the
disease.There are different kinds of breast cancer. The kind of
breast cancer depends on which cells in the breast turn into
cancer.Breast cancer can begin in different parts of the breast.
A breast is made up of three main parts: lobules, ducts, and
connective tissue. The lobules are the glands that produce milk.
The ducts are tubes that carry milk to the nipple. The
connective tissue (which consists of fibrous and fatty tissue)
surrounds and holds everything together. Most breast cancers
begin in the ducts or lobules.
Breast cancer can spread outside the breast through blood

3. vessels and lymph vessels. When breast cancer spreads to other
parts of the body, it is said to have metastasized. Most breast
cancer are adenocarcinomas.
The most common kinds of breast cancer are
· Invasive ductal carcinoma. The cancer cells grow outside the
ducts into other parts of the breast tissue. Invasive cancer cells
can also spread, or metastasize, to other parts of the body.
· Invasive lobular carcinoma. Cancer cells spread from the
lobules to the breast tissues that are close by. These invasive
cancer cells can also spread to other parts of the body.
There are several other less common kinds of breast cancer,
such as Paget’s disease , r medullary, mucinous, and
inflammatory breast cancer.
Early inflammatory breast cancer may include persistent itching
and the appearance of a rash or small irritation similar to an
insect bite. The breast typically becomes red, swollen, and
warm. The skin may appear pitted like an orange peel, and
nipple changes such as inversion, flattening, or dimpling may
occur.
Ductal carcinoma in situ (DCIS) is a breast disease that may
lead to breast cancer. The cancer cells are only in the lining of
the ducts and have not spread to other tissues in the breast.
The main factors that influence your breast cancer risk are
being a woman and getting older. Other risk factors include—
· Changes in breast cancer-related genes (BRCA1 or BRCA2).
· Having your first menstrual period before age 12.
· Never giving birth or being older when your first child is
born.
· Starting menopause after age 55.
· Taking hormones to replace missing estrogen and progesterone
in menopause for more than five years.
· Taking oral contraceptives (birth control pills).
· A personal history of breast cancer, dense breasts, or some
other
breast problems.
· A family history of breast cancer (parent, sibling, or child).

4. · Getting radiation therapy to the breast or chest.
· Being overweight, especially after menopause.
While BRCA1 and BRCA2 gene mutations may increase your
odds of developing breast cancer, your odds of having either
mutation are pretty small. An estimated 0.25% of the general
population carries a mutated BRCA gene, or about one out of
every 400 people.
If one of your parents has a BRCA mutation, you have a 50%
chance of inheriting the mutated gene.
Odds can also vary depending on a person’s ethnicity. For
example, people of Ashkenazi Jewish descent have a 2.5%
chance of inheriting a BRCA mutation, or about 10 times the
rate of the general population. It’s estimated that 55 – 65% of
women with the BRCA1 mutation will develop breast cancer
before age 70. Approximately 45% of women with a BRCA2
mutation will develop breast cancer by age 70.
Some things may increase your risk
The main factors that influence your breast cancer risk are
being a woman and getting older. Other risk factors include—
· Changes in breast cancer-related genes (BRCA1 or BRCA2).
· Having your first menstrual period before age 12.
· Never giving birth, or being older when your first child is
born.
· Starting menopause after age 55.
· Taking hormones to replace missing estrogen and progesterone
in menopause for more than five years.
· Taking oral contraceptives (birth control pills).
· A personal history of breast cancer, dense breasts, or some
other
breast problems.
· A family history of breast cancer (parent, sibling, or child).
· Getting radiation therapy to the breast or chest.
· Being overweight, especially after menopause.
Pathology

5. Most breast cancers are epithelial tumors that develop from
cells lining ducts or lobules; less common are nonepithelial
cancers of the supporting stroma (eg, angiosarcoma, primary
stromal sarcomas, phyllodes tumor).
Cancers are divided into carcinoma in situ and invasive cancer.
Carcinoma in situ is proliferation of cancer cells within ducts or
lobules and without invasion of stromal tissue. There are 2
types:
· Ductal carcinoma in situ (DCIS): About 85% of carcinoma in
situ are this type. DCIS is usually detected only by
mammography. It may involve a small or wide area of the
breast; if a wide area is involved, microscopic invasive foci may
develop over time.
· Lobular carcinoma in situ (LCIS): LCIS is often multifocal
and bilateral. There are 2 types: classic and pleomorphic.
Classic LCIS is not malignant but increases risk of developing
invasive carcinoma in either breast. This nonpalpable lesion is
usually detected via biopsy; it is rarely visualized with
mammography. Pleomorphic LCIS behaves more like DCIS; it
should be excised to negative margins.
Invasive carcinoma is primarily adenocarcinoma. About 80% is
the infiltrating ductal type; most of the remaining cases are
infiltrating lobular. Rare types include medullary, mucinous,
metaplastic, and tubular carcinomas. Mucinous carcinoma tends
to develop in older women and to be slow growing. Women with
these rare types of breast cancer have a much better prognosis
than women with other types of invasive breast cancer.
Inflammatory breast cancer is a fast-growing, often fatal cancer.
Cancer cells block the lymphatic vessels in breast skin; as a
result, the breast appears inflamed, and the skin appears
thickened, resembling orange peel (peau d’orange). Usually,
inflammatory breast cancer spreads to the lymph nodes in the
armpit. The lymph nodes feel like hard lumps. However, often
no mass is felt in the breast itself because this cancer is
dispersed throughout the breast.

6. Paget disease of the nipple (not to be confused with the
metabolic bone disease also called Paget disease) is a form of
ductal carcinoma in situ that extends into the skin over the
nipple and areola, manifesting with a skin lesion (eg, an
eczematous or a psoriaform lesion). Characteristic malignant
cells called Paget cells are present in the epidermis. Women
with Paget disease of the nipple often have underlying invasive
or in situ cancer.
Pathophysiology
Breast cancer invades locally and spreads through the regional
lymph nodes, bloodstream, or both. Metastatic breast cancer
may affect almost any organ in the body—most commonly,
lungs, liver, bone, brain, and skin.
Most skin metastases occur near the site of breast surgery; scalp
metastases are also common. Metastatic breast cancer frequently
appears years or decades after initial diagnosis and
treatment.Hormone receptors
Estrogen and progesterone receptors, present in some breast
cancers, are nuclear hormone receptors that promote DNA
replication and cell division when the appropriate hormones
bind to them. Thus, drugs that block these receptors may be
useful in treating tumors with the receptors. About two thirds of
postmenopausal patients with cancer have an estrogen-receptor
positive (ER+) tumor. Incidence of ER+ tumors is lower among
premenopausal patients.
Another cellular receptor is human epidermal growth factor
receptor 2 (HER2; also called HER2/neu or ErbB2); its presence
correlates with a poorer prognosis at any given stage of cancer.
In about 20% of patients with breast cancer, HER2 receptors are
overexpressed. Drugs that block these receptors are part of
standard treatment for these patients.
Some warning signs of breast cancer are—
· New lump in the breast or underarm (armpit).
· Thickening or swelling of part of the breast.

7. · Irritation or dimpling of breast skin.
· Redness or flaky skin in the nipple area or the breast.
· Pulling in of the nipple or pain in the nipple area.
· Nipple discharge other than breast milk, including blood.
· Any change in the size or the shape of the breast.
· Pain in the breast.
Symptoms of breast tumors vary from person to person. Very
often breast tumor discovered by patient as breast mass or
during routine physical examination or mammography. Some
common, early warning signs of breast cancer include:
· Skin changes, such as swelling, redness, or other visible
differences in one or both breasts
· An increase in size or change in shape of the breast(s)
· Changes in the appearance of one or both nipples
· Nipple discharge other than breast milk
· General pain in/on any part of the breast
· Lumps or nodes felt on or inside of the breast
Symptoms more specific to invasive breast cancer are:
· Irritated or itchy breasts
· Change in breast color
· Increase in breast size or shape (over a short period of time)
· Changes in touch (may feel hard, tender or warm)
· Peeling or flaking of the nipple skin
· A breast lump or thickening
· Redness or pitting of the breast skin (like the skin of an
orange)
Symptoms and Signs
Many breast cancers are discovered as a mass by the patient or
during routine physical examination or mammography. Less
commonly, the presenting symptom is breast pain or
enlargement or a nondescript thickening in the breast.
Paget disease of the nipple manifests as skin changes, including
erythema, crusting, scaling, and discharge; these changes
usually appear so benign that the patient ignores them, delaying
diagnosis for a year or more. About 50% of patients with Paget
disease of the nipple have a palpable mass at presentation.

8. A few patients with breast cancer present with signs of
metastatic disease (eg, pathologic fracture, pulmonary
dysfunction).
A common finding during physical examination is asymmetry or
a dominant mass—a mass distinctly different from the
surrounding breast tissue. Diffuse fibrotic changes in a quadrant
of the breast, usually the upper outer quadrant, are more
characteristic of benign disorders; a slightly firmer thickening
in one breast but not the other may be a sign of cancer.
More advanced breast cancers are characterized by one or more
of the following:
· Fixation of the mass to the chest wall or to overlying skin
· Satellite nodules or ulcers in the skin
· Exaggeration of the usual skin markings resulting from skin
edema caused by invasion of dermal lympha tic vessels (so-
called peau d’orange)
Matted or fixed axillary lymph nodes suggest tumor spread, as
does supraclavicular or infraclavicular lymphadenopathy.
Inflammatory breast cancer is characterized by peau d'orange,
erythema, and enlargement of the breast, often without a mass.
A nipple discharge is common. Inflammatory breast cancer has
a particularly aggressive
According to the American Cancer Society, when breast cancer
is detected early, and is in the localized stage, the 5-year
relative survival rate is 99%. Early detection includes doing
monthly breast self-exams and scheduling regular clinical breast
exams and mammograms.
References
American Cancer Society. Breast cancer facts & figures. 2019.
https://www.cancer.org/research/cancer-facts-statistics/breast-
cancer-facts-figures.html

9. Gorham, R. (2020). Caring for women on adjuvant therapy for
breast cancer: Role of the NP in the primary care
setting. Women’s Healthcare: A Clinical Journal for NPs, 8(1),
6–16.
Center for Disease Control and Prevention (2019).
https://www.cdc.gov/cancer/breast/pdf/BreastCancerFactSheet.p
df
Center for Disease Control and Prevention. (2016). Leading
cancer cases and deaths, female, 2016. Retrieved from
https://gis.cdc.gov/Cancer/USCS/DataViz.html
Kosir, M. A. (2019). Breast Cancer. Merck Manuals
Professional Edition. Retrieved
https://www.merckmanuals.com/professional/gynecology-and-
obstetrics/breast-disorders/breast-cancer#
Below is a brief summary of my research:
Supporting prescribing in older patient with multimorbidity in
primary care (SPPiRE) is a cluster randomised controlled trial
that was designed to assess the effectiveness of a web guided
medication review in reducing potentially inappropriate
prescribing and polypharmacy in patients aged ≥ 65 years who

10. are prescribed ≥ 15 medicines, in Irish primary care.
I suggest you review your EBM notes about randomised
controlled trial design. This is a cluster randomised controlled
trial, meaning groups or “clusters” are randomised together.
This is done to avoid contamination, as the intervention is being
delivered by GPs and it would be difficult for a GP to treat their
own patients differently. Each GP practice is randomised as one
I also suggest you look up the CONSORT reporting
requirements for randomised controlled trials.
Population:
Patients aged ≥ 65 years who are prescribed ≥ 15 medicines, in
Irish primary care
Intervention:
Web guided medication review and professional training videos
Control:
Usual GP care
Outcome measures:
Primary outcome measure:
Number of repeat medicines
Proportion of patients with at least 1 PIP
Secondary outcome measures:
Health related quality of life
Multimorbidity treatment burden questionnaire
Patients attitudes to deprescribing
GP reported health care utilisation
I suggest that your literature review should be on medication
review guidelines and the evidence for medication reviews.
Here is a recommended reading list for your literature review:
· https://www.ncbi.nlm.nih.gov/pubmed/28764753 (the trial’s
protocol)
·

11. https://www.icgp.ie/speck/properties/asset/asset.cfm?type=Libra
ryAsset&id=0329F12C%2D4355%2D4E18%2D8DC194DF812D
B2E7&property=asset&revision=tip&disposition=inline&app=ic
gp&filename=Med%5FReview%5FQRG%2Epdf (Irish College
of General Practitioners quick reference guide on medication
reviews, this document will give an overview on what
potentially inappropriate prescribing is, and why it is important
to address).
· https://www.ncbi.nlm.nih.gov/pubmed/17630041 (review
article on appropriate prescribing and polypharmacy in the
elderly)
· https://www.ncbi.nlm.nih.gov/pubmed/27321600 (Systematic
review on interventions to improve prescribing in the elderly)
· https://www.ncbi.nlm.nih.gov/pubmed/22500541 (review
article on “deprescribing”)
I also suggest you look at the following clinical guidelines in
addition to the ICGP medication review reference guide above:
SIGN Polypharmacy guidelines
NICE multimorbidity guidelines
NICE medication optimisation guidelines