Immune System Disorders

Chederline Simeon
Rasmussen College
Physical Assessment
Professor Shaun Creary-Walker
January 16, 2021
I contacted Jane Dawns, for a knowledgeable discussion based on her experience as a patient
diagnosed with breast cancer. She has lived with this diagnosis for the last two years and is
considered well informed on her diagnosis due to the amounts of research she has done on her
condition both online and having countless conversations with her oncologists.
Interview
INTERVIEWER: Which immune system disorder do you have?

INTERVIEWEE: I was diagnosed with early stage-3 breast cancer.

INTERVIEWER: How long have you had this disorder?

INTERVIEWEE: the disease was diagnosed since 2years, but the symptoms started around
6months before the disease was diagnosed.

INTERVIEWER: How has this disorder changed your homme and work life?

INTERVIEWEE: I lead a disciplined life after treatment. I am conscious of a work-life balance,

I eat on time, eat right, and practice yoga regularly. I try to have sound sleep for seven-eight
hours. I continue giving my best at the work place. I ate as per a plan. All home-made, freshly
prepared food with low amounts of spice and oil. A well-chosen diet of fruits and vegetables was
helping build my immune system. I repented for not having taken care of my body for years. I
feel my disease, to a great extent, was because of my wrong lifestyle. I placed others and their
needs above myself. Every woman should take control of their health and accord it the highest
priority.

INTERVIEWER: Are you able to carry out daily activities independently?

INTERVIEWEE:  I hired a part-time cook while trying to attend to other daily chores
independently. This added to my self-worth and boosted my confidence. I continued to work for
my company remotely. Let the patient decide their daily routine, as each body behaves
differently to the treatment.

INTERVIEWER: What therapies are you using to manage this disorder?

INTERVIEWEE: Initially total mastectomy followed by six weeks of radiation therapy along
with chemotherapy.

INTERVIEWER: What, if any, side effects does the treatment have?

INTERVIEWEE: I felt very tired and had continual crops of mouth ulcers. From the second
week of my chemo I started shedding hair. It came out in bunches the after-effects of chemo are
paralyzing.
INTERVIEWER: Has this disorder changed your body?
INTERVIEWEE: From the second week of my chemo I started shedding hair. It came out in
bunches. I cried a lot. Honestly, this was the worst part of my treatment. It made me conscious of
my self-image. I started drawing the curtains of the windows at home so that no one would see
me. I tried using a wig but rejected it soon. I would gaze into the mirror for a long time, feeling
lost and helpless. But eventually, I realized that I am more than my looks. So, don’t fret over the
loss of your hair. The hair will definitely grow back.

INTERVIEWER: Does this disorder have any emotional effects on you?

INTERVIEWEE: Utter disbelief, fear and questioning. I had done all the right things, had 3
children before my 30th birthday, breast fed them all, never smoked or drank or used the
contraceptive pill. Why me? I cried a lot, feeling lost and helpless.  The mind is incredibly
powerful when it comes to healing through positive thinking and by letting go of resentment.

INTERVIEWER: Have you tried any alternative therapies, such as Eastern medicine like
acupuncture and herbal treatments.

INTERVIEWEE: I have not tried any alternative methods of treatment. I believe that alternative
methods, if desired, should complement and not substitute conventional methods of treatment.
But I practice yoga regularly.

Breast Cancer
Breast cancer is the most common invasive cancer in women and the second leading cause of
cancer death in women after lung cancer. Breast cancer is the most frequent malignancy in
women worldwide and is curable in ~70–80% of patients with early-stage, non-metastatic
disease. Advanced breast cancer with distant organ metastases is considered incurable with
currently available therapies. On the molecular level, breast cancer is a heterogeneous disease;
molecular features include activation of human epidermal growth factor receptor 2 (HER2,
encoded by ERBB2), activation of hormone receptors (estrogen receptor and progesterone
receptor) and/or BRCA mutations. Treatment strategies differ according to molecular subtype.
Management of breast cancer is multidisciplinary; it includes locoregional (surgery and radiation
therapy) and systemic therapy approaches. Systemic therapies include endocrine therapy for
hormone receptor-positive disease, chemotherapy, anti-HER2 therapy for HER2-positive
disease, bone stabilizing agents, poly (ADP-ribose) polymerase inhibitors for BRCA mutation
carriers and, quite recently, immunotherapy. Future therapeutic concepts in breast cancer aim at
individualization of therapy as well as at treatment de-escalation and escalation based on tumor
biology and early therapy response. Next to further treatment innovations, equal worldwide
access to therapeutic advances remains the global challenge in breast cancer care for the future.

Symptoms
The first symptoms of breast cancer usually appear as an area of thickened tissue in the breast or
a lump in the breast or an armpit.
Other symptoms include:

pain in the armpits or breast that does not change with the monthly cycle
pitting or redness of the skin of the breast, similar to the surface of an orange
a rash around or on one of the nipples
discharge from a nipple, possibly containing blood
a sunken or inverted nipple
a change in the size or shape of the breast
peeling, flaking, or scaling of the skin on the breast or nipple
Most breast lumps are not cancerous. However, women should visit a doctor for an
examination if they notice a lump on the breast.

Stages

A doctor stages cancer according to the size of the tumor and whether it has spread to lymph
nodes or other parts of the body.

There are different ways of staging breast cancer. One way is from stage 0–4, with
subdivided categories at each numbered stage. Descriptions of the four main stages are listed
below, though the specific substage of a cancer may also depend on other specific
characteristics of the tumor, such as HER2 receptor status.

Stage 0: Known as ductal carcinoma in situ (DCIS), the cells are limited to within the
ducts and have not invaded surrounding tissues.
Stage 1: At this stage, the tumor measures up to 2 centimeters (cm) across. It has not
affected any lymph nodes, or there are small groups of cancer cells in the lymph nodes.
Stage 2: The tumor is 2 cm across, and it has started to spread to nearby nodes, or is 2–5
cm across and has not spread to the lymph nodes.
Stage 3: The tumor is up to 5 cm across, and it has spread to several lymph nodes or the
tumor is larger than 5 cm and has spread to a few lymph nodes.
Stage 4: The cancer has spread to distant organs, most often the bones, liver, brain, or
lungs.

BREAST CANCER AND PATHOPHYSIOLOGY

Breast cancer is a malignant tumor that starts in the cells of the breast. Like other cancers,
there are several factors that can raise the risk of getting breast cancer. Damage to the DNA
and genetic mutations can lead to breast cancer have been experimentally linked to estrogen
exposure. Some individuals inherit defects in the DNA and genes like the BRCA1, BRCA2
and P53 among others. Those with a family history of ovarian or breast cancer thus are at an
increased risk of breast cancer.

The immune system normally seeks out cancer cells and cells with damaged DNA and
destroys them. Breast cancer may be a result of failure of such an effective immune defence
and surveillance.
These are several signaling systems of growth factors and other mediators that interact
between stromal cells and epithelial cells. Disrupting these may lead to breast cancer as well.

TREATMENT
Surgery:
Breast-conserving surgery (BSC): also known as lumpectomy or wide local excision, BSC
involves resection of the tumor along with a margin of tissue while conserving the cosmetic
appearance of the breast. Most breast surgeries are of this type because (i) most tumors are
locally invasive and (ii) large primary tumors can be reduced in size by neoadjuvant
chemotherapy prior to conservative surgery.

Mastectomy: surgical removal of entire breast, including the fascia over the pectoralis
muscles. Surgeons may preserve some skin and the nipple/areola for reconstruction. The
indication for mastectomy is multicentric invasive carcinoma, inflammatory carcinoma, or
extensive intraductal carcinomas.
.
Axillary lymph node dissection: removal of the lymph nodes draining the breast tissue for
lymph node micro metastasis. This is done at the same time as BSC or mastectomy.
However, recent evidence suggests that axillary lymph node biopsy is unnecessary regardless
of whether the sentinel lymph node biopsy is negative or positive because there is no
mortality benefit.

Adjuvant therapy
cytotoxic chemotherapy, endocrine therapy, or radiation therapy may be used post-surgery to
prevent relapse.

Radiation therapy
Either whole or partial breast irradiation may be used (see Carcinogenesis chapter for
mechanism of radiation therapy). Adjuvant radiation therapy is applied post-BCS or post-
mastectomy to prevent recurrence. Since most recurrence of early-stage breast cancer occurs
locally, partial irradiation at the tumor site has similar mortality benefits as whole breast
irradiation. However, new evidence suggests an increased risk of local and axillary
recurrence with partial irradiation.
Radiation of metastatic disease (e.g. bone or brain metastases) is also used.

Endocrine therapy
Breast cancer is a hormone-sensitive cancer. Most breast cancer cells are ER-positive, and
thus will respond to reduction of circulating estrogens. HR-negative breast cancers will not
respond to endocrine therapy.
Mainly used as (i) adjuvant therapy for early-stage hormone-sensitive breast cancer or as (ii)
first line therapy for metastatic hormone-sensitive breast cancer.
Cancer Care Ontario recommends 5 years of adjuvant endocrine therapy for early-stage
breast cancer in postmenopausal women.
Antiestrogens (e.g. tamoxifen): Competitively binds ER and inhibits estrogen binding.

Aromatase inhibitors: Aromatase, also known as estrogen synthase, is an enzyme responsible

for estrogen synthesis. There are two types: steroidal (type I) and non-steroidal (type II). The
steroidal type (e.g. exemestane) is an androgen analogue that binds permanently with the
aromatase enzyme, leading to long-term and specific inhibition of the enzyme. The non-
steroidal type (e.g. anastrozole and letrozole) originates from an anti-epileptic drug that
reversibly binds and inhibits the cytochrome P450 unit in aromatase. Because the non-
steroidal type has a good molecular fit with the substrate-binding site, it is more potent than
the steroidal type. Both types have good efficacy and high specificity for the aromatase
enzyme.

Ovarian ablation:
induction of artificial menopause by ovariectomy significantly reduces breast cancer risk.
Adrenalectomy eliminates a source of androgens in females, which is the precursor to
aromatase-derived estrogens. However, these surgical approaches are irreversible and cause
major side effects, so they are less often used.
Ovarian suppression: LHRH (GnRH) agonist (e.g. goserelin and leuprorelin) can be used to
reversibly suppress LH/FSH release and thus estrogen release.

Chemotherapy

Cytotoxic drugs, such as cyclophosphamide, methotrexate, doxorubicin, and paclitaxel, are

used in hormone receptor-negative or HER2-positive breast cancers. They can either be
given pre-surgery as neoadjuvant to shrink the tumor or post-surgery as adjuvant to prevent
relapse.

ARTICLES FOR RERERENCE

Pérou, C. M. et al. Molecular portraits of human breast tumors. Nature 406, 747–752 (2000).
Cardoso, F. et al. European Breast Cancer Conference manifesto on breast centers/units. Eur.
J. Cancer 72, 244–250 (2017).

Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and
mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394–424 (2018).